Continuous renal replacement therapy (CRRT) is an important treatment for critically ill patients. Critically ill patients often need to receive antimicrobials and CRRT treatments at the same time. CRRT affects the pharmacokinetics and pharmacodynamics of antimicrobials, and there is a lack of recommendations and suggestions for the antimicrobial dosing during CRRT. The clinical medicine, pharmacy, intensive care and infectious diseases specialists in China set up an expert group on antimicrobial dosing optimization during CRRT, conducted evidence search around CRRT factors, drug characteristics, patient factors and antimicrobial dosing optimization during CRRT, and fully discussed and formulated the consensus, to provide guiding advices on the rational use of antimicrobials during CRRT.

Diabetes is a major risk factor for chronic kidney disease (CKD). Finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, has been confirmed to have a definite renal and cardiovascular protective effect on diabetes mellitus with CKD. Long-term use can significantly reduce the urinary albumin to creatinine ratio in patients with diabetes mellitus and has little effect on blood potassium. In order to make the clinical application of finerenone more reasonable and standardized, based on research evidence and clinical practice experience, the expert group formed the Chinese expert consensus on the use of finerenone in patients with diabetes mellitus and CKD after many discussions. The mechanism of action and pharmacological properties of finerenone, evidence-based medical evidence, suitable population, specific usage and precautions were described, and 27 recommendations were formed to provide reference for clinical use of finerenone and benefit patients.

Sodium-glucose transporter 2 (SGLT2) inhibitors are a novel type of oral hypoglycemic agent. Clinical trials have found that these drugs not only help control diabetes but also provide additional benefits for heart and kidney outcome. They have shown cardiorenal protection in patients with type 2 diabetes and can improve outcomes in non-diabetic patients with chronic kidney disease (CKD), and the overall safety performance is good. Therefore, SGLT2 inhibitors have become important drugs for cardiorenal protection in CKD patients. The consensus expert group undertook an extensive process to develop this consensus on the use of SGLT2 inhibitor drugs in managing CKD. They engaged multidisciplinary experts from nephrology, endocrinology, and cardiology to ensure a comprehensive and standardized approach. The expert group utilized existing evidence-based evidence and the expertise of the participating clinicians to formulate this consensus through consultation, voting and discussion. The consensus includes the recommended population for SGLT2 inhibitors use, the risk assessment of adverse reactions before use, the recommendation of combination administration, and the monitoring and management of adverse reactions during use. This collaborative effort aims to provide physicians with a reliable and practical framework for the rational use of SGLT2 inhibitor drugs in clinical practice.

Recent studies have revealed that fluid overload is an independent risk factor for increasing renal function impairment, decreasing renal recovery rate and increasing mortality in severe patients with acute kidney injury (AKI), acute respiratory distress syndrome,or sepsis. The damage of fluid overload on renal function may be related to renal venous hypertension and renal interstitial edema, and eventually lead to the decrease of renal blood flow and glomerular filtration rate. However, fluid clearance with diuretics or continuous renal replacement therapy (CRRT) may increase the risk of hypovolemia, hemodynamic instability, and tissue and organ hypoperfusion. Therefore, accurate fluid volume status assessment and management in AKI patients during CRRT is critical. The expert group of Chinese Society of Nephrology formulated this expert consensus on fluid volume assessment and management in CRRT based on evidence-based medical evidence and clinical experience. Through systematic and comprehensive literature search, data analysis and professional discussion in this field, the expert group constructed five special topics on fluid volume management in CRRT: the pathophysiological basis and harm of fluid volume imbalance in AKI patients, the management strategies on fluid volume in AKI patients, the assessment on fluid volume status and reactivity in AKI patients, the grading and application of fluid volume management in CRRT, and the management target and prescription on fluid volume in CRRT. This consensus aims to standardize clinical operations, reduce the incidence of fluid volume imbalances in AKI patients, and improve the patients' prognosis.

It was a retrospective cohort study. Patients diagnosed with idiopathic membranous nephropathy (IMN) and received rituximab (RTX) alone for one course of treatment during hospitalization in the Department of Nephrology of the First Hospital of Jilin University from March 2020 to March 2022 were enrolled. The patients were divided into 1 g standard treatment group (once 1 g every 2 weeks for twice) and 375 mg/m² experimental treatment group (375 mg/m² once a week for 4 weeks) according to the different methods of drug administration, and the efficacy and safety of different doses of RTX in the treatment of IMN were compared between the two groups to provide a reference for optimizing the clinical treatment protocol. The patients were followed up regularly for more than 9 months after treatment and the data were complete. A total of 69 patients were included with age of (51.7±11.8) years old, and 46 males (66.7%). There were 31 patients in the 1 g standard treatment group and 38 patients in the 375 mg/m² experimental treatment group. The proportion of first-treatment patients in the 1 g standard treatment group was higher than that in the 375 mg/m² experimental treatment group (87.1% vs. 65.8%, χ ²=4.174, P=0.041). There were no statistically significant differences in the general data, clinical characteristics and baseline laboratory parameters between the two groups (all P>0.05). At the end of 3 months of treatment, 22 patients (31.9%) experienced remission, including 9 patients (29.0%) in the 1 g standard treatment group and 13 patients (34.2%) in the 375 mg/m² experimental treatment group (χ ²=0.211, P=0.646). At 6 months, 30 patients (43.5%) experienced remission, including 12 patients (38.7%) in the 1 g standard treatment group and 18 patients (47.4%) in the 375 mg/m² experimental treatment group (χ ²=0.521, P=0.470). At 9 months, 38 patients (55.1%) achieved remission, including 18 patients (58.1%) in the 1 g standard treatment group and 20 patients (52.6%) in the 375 mg/m² experimental treatment group (χ ²=0.204, P=0.652). At 9 months, the 24 h urine protein of 1 g standard treatment group and 375 mg/m² experimental treatment group decreased by 7.93 (6.24, 8.46) g and 7.45 (5.66, 8.67) g (both P<0.05), respectively, and serum albumin increased by 16.4 (15.5, 17.5) g/L and 15.5 (9.0, 15.8) g/L (both P<0.05), respectively, from the baseline value. Kaplan-Meier survival analysis result showed that there was no significant difference in the time of phospholipase A2 receptor titer decreasing to <5 RU/ml between the two groups (Log-rank χ ²=3.653, P=0.056). Twenty-three non-serious adverse events occurred in the 1 g standard treatment group, involving 16 patients, and 10 non-serious adverse events occurred in the 375 mg/m² experimental treatment group, involving 10 patients. There was better safety in the 375 mg/m² experimental treatment group than that in the 1 g standard treatment group (Fisher value=8.593, P=0.015). Both 375 mg/m² regimen and 1 g regimen of RTX in IMN patients are effective in relieving proteinuria and elevating serum albumin. The 375 mg/m² regimen of RTX has a lower incidence of adverse events compared with the 1 g regimen.

Chronic kidney disease (CKD) is a serious health problem worldwide, whereas there is still no efficient cure. The gut microbiota plays a crucial role in maintaining human health and disease resistance, and multiple studies have confirmed that the gut microbiota is closely related to the occurrence and development of CKD. Starting from the "gut-kidney axis" theory, this article provides a systematic review of the changes in gut microbiota composition and function in patients with CKD, such as a decrease in the abundance of butyrate-producing bacteria Roseburia and Faecalibacterium prausnitzii. Besides that, the article explores the mechanisms by which the gut microbiota affects CKD progression, such as inflammation and immunity, and also describes the application methods of using the gut microbiota as a therapeutic target for CKD, such as fecal microbiota transplantation, microecologics, and dietary therapy, in order to provide microbial- based targets for the clinical diagnosis and treatment of CKD.

Erythropoiesis-stimulating agents (ESAs) are commonly used drugs in the treatment of renal anemia. There are currently two types of ESAs available to clinicians, including short-acting ESAs and long-acting ESAs. Short-acting ESAs have been used for decades in China, which are being widely accepted nowadays. Several professional societies have published consensus guidelines for the use and interpretation of short-acting ESAs worldwide in recent years. The advantages of long-acting ESAs include long half-life, low infusion frequency, good patient compliance, etc. There is still a lack of guidance on the clinical use of long-acting ESAs although important progress of long-acting ESAs has been made in clinical trials in recent years. Thus, the Society of Nephrology & Dialysis of China Non-Government Medical Institutions Association organized relevant experts to jointly formulate the "Chinese Expert Consensus on Long-acting ESAs in the Treatment of Renal Anemia". This consensus mainly introduces the classification, mechanism of action and pharmacological characteristics of long-acting ESAs, their indications, timing, administration protocols, application in special populations, adverse reactions and management in renal anemia. It is the hope of this concensus will guide the clinical use of long-acting ESAs in the treatment of renal anemia.

Objective To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4. Methods It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients. Results A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR (OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI (OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin (OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP (OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes damage to multiple vital tissues and target organs, and lupus nephritis (LN) is a serious complication of SLE involving the kidneys. The use of glucocorticoids and immunosuppressants has been dominant in the treatment strategy of LN, while their adverse effects have also raised concerns. In recent years, the development and use of biologics have provided new ideas for the treatment of LN and have also achieved positive efficacy in several clinical trials in SLE and LN. Biologics can be divided into monoclonal antibodies and recombinant proteins, which exert therapeutic effects on SLE and LN through a variety of mechanisms at the cellular-molecular level. In this article, we review recent research advances in the treatment of SLE and LN from the perspective of the different mechanisms of action of biologics.

Objective To study the incidence and risk factors of central vein stenosis (CVS) in chronic kidney disease (CKD) patients who received arteriovenous fistula (AVF) creation for the first time, as well as effects of CVS on patency of ipsilateral AVF. Methods It was a retrospective study. The CKD patients who received AVF creation for the first time in the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2020, with central vein digital subtraction angiography (DSA) results prior to angioplasty were selected as the study subjects. The differences of incidence of CVS in CKD patients with/without a history of cervical catheterization and primary patency rates of AVF between CVS and non-CVS groups were compared. Logistic regression analysis method was applied to analyze the influencing factors of CVS in CKD patients. Kaplan-Meier method was used to analyze the primary patency rate of AVF. Cox regression analysis method was used to analyze the effect of CVS on the primary patency of ipsilateral AVF. Results A total of 283 CKD patients aged (50.45±14.76) years were enrolled in the study, including 165 males (58.3%). The dialysis age was 0.5 (0, 7.0) months. There were 55 patients (19.4%) diagnosed with CVS before AVF, including 39 patients with stenosis <50% and 16 patients with stenosis ≥50%. The incidence of CVS in patients with history of right internal jugular vein central venous catheter insertion was significantly higher than that in those without this history [60.5% (26/43) vs. 9.9% (15/151), χ²=51.274, P<0.001]. Multivariate logistic regression analysis results showed that hemodialysis catheters indwelling time ≥3 months elevated the risk of CVS (OR=4.345, 95% CI 1.540-12.263, P=0.006). A subset of 268 patients who had AVF creation ipsilateral to CVS were analyzed to determine the effects of CVS on patency of AVF. The median follow-up time was 34 months. The primary patency rate of AVF in the moderate to severe CVS group was significantly lower than that in the non-CVS group (5/7 vs. 58/228, χ²=7.720, P=0.005). The primary patency rates of AVF in the subclavian vein stenosis group and superior vena cava stenosis group were significantly lower than those in the brachiocephalic vein stenosis group (4/5 vs. 8/27, χ² =6.974, P=0.008; 6/8 vs. 8/27, χ² =6.908, P=0.009, respectively). Moderate to severe CVS and combined diabetes were independent influencing factors of primary patency of AVF (HR=4.362, 95% CI 1.644-11.574, P=0.003; HR=2.682, 95% CI 1.624-4.431, P<0.001, respectively). Conclusions The incidence of CVS is higher in CKD patients who establish an arteriovenous fistula for the first time. Hemodialysis catheter indwelling time ≥3 months is an independent risk factor of CVS. The moderate to severe CVS is an independent risk factor of primary patency of AVF.

Objective To explore the changes of disease burden and risk factors of chronic kidney disease (CKD) due to type 1 and type 2 diabetes mellitus in China from 1990 to 2019, and to provide reference data for the prevention and control of diabetic kidney disease (DKD). Methods The Chinese DKD data were obtained from the 2019 Global Burden of Disease (GBD) database. The morbidity, prevalence, mortality, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life year (DALY) were used to compare the disease burden of CKD due to type 1 and type 2 diabetes mellitus from 1990 to 2019. In addition, the risk factors of DKD were analyzed. Results The numbers of CKD patients due to type 1 and type 2 diabetes mellitus in China were 574 (95% UI 495-665) and 31 076 (95% UI 28 152-33 909) thousand, and the numbers of new cases were 9 (95% UI 8-11) and 434 (95% UI 390-481) thousand in 2019, respectively. The numbers of death were 13 (95% UI 8-18) and 63 (95% UI 50-77) thousand, respectively. The age groups with the largest number of patients and new cases of CKD due to type 1 diabetes mellitus were 30-34 years old and <5 years old, respectively. The age group with the largest number of patients and new cases of CKD due to type 2 diabetes mellitus were 50-54 years old and 70-74 years old, respectively. From 1990 to 2019, the age-standardized prevalence rate of DKD patients in China was relatively stable, but the age-standardized incidence rate and YLD rate showed an upward trend, while the age-standardized mortality rate, YLL rate, and DALY rate showed a downward trend. The main risk factors associated with DKD death were high fasting plasma glucose, kidney dysfunction, high systolic blood pressure, high body mass index, high sodium diet, and lead exposure. The proportions of DKD death caused by high systolic blood pressure and high body mass index in the Chinese population were still increasing. Conclusions From 1990 to 2019, the age-standardized incidence and YLD rate of DKD in China shows an upward trend, while the age-standardized prevalence rate is relatively stable, and the age-standardized mortality rate, YLL rate, and DALY rate show a decreasing trend. High fasting glucose, renal failure, high systolic blood pressure, high body mass index, high sodium diet, and lead exposure are risk factors associated with death in DKD patients. With the progress of aging, the disease burden of DKD in China will continuously increase. Future work should be focused on population-specific interventions, taking into consideration the risk factors identified within the study.

As a home treatment and economical and practical treatment mode, peritoneal dialysis (PD) is an effective renal replacement therapy for end-stage kidney disease. The number of PD patients in the world is increasing, and prognosis has been significantly improved. However, compared with the general population, the quality of life of PD patients is not satisfactory, and the disease burden is still very high. There is significant heterogeneity in the reports of clinical outcomes of PD in different countries and regions. The heterogeneity seriously affects the validity of clinical research evidence and the continuous improvement of the quality of PD centers. New progress has been made in the study of standardized clinical outcome of PD in recent years. The article reviews the heterogeneity of PD clinical outcome report, standardized clinical outcome classification and core outcome to standardize the report of PD clinical outcome, improve the clinical research quality and management level of PD, and finally improve the prognosis of patients.

Diabetic kidney disease (DKD) is a primary cause of chronic kidney disease and end-stage renal disease, as well as one of the most common microvascular consequences of diabetes mellitus. Obesity, as a metabolic disease, has a substantial impact on the onset and progression of DKD. Epidemiological studies have revealed obesity is a risk factor of DKD and end-stage renal disease, which can promote the occurrence and progression of DKD through various mechanisms, including alterations in hemodynamics, metabolic regulation, and chronic inflammation. Clinical researches also have demonstrated the importance of various weight loss interventions in the prevention and management of DKD. Therefore, gaining a deeper understanding of the correlation between obesity and DKD will contribute to improving the prognosis and quality of life of individuals with diabetes mellitus. The paper reviews the relationship between obesity and DKD on the epidemiological characteristics of obesity and DKD, the potential mechanism of obesity affecting DKD and the influence of obesity intervention on DKD.

Chronic kidney disease-associated pruritus (CKD-aP), one of the most common and intolerable complications in hemodialysis patients, not only seriously affects patients' quality of life and physical and mental health, but also increases the risk of long-term mortality. The pathogenesis of CKD-aP remains unclear, and immune-inflammatory dysregulation, imbalance of endogenous opioid system, abnormal accumulation of metabolites, xerosis, abnormal histamine level as well as hyperparathyroidism, have all been shown to be associated with pruritus. There is a lack of satisfactory and effective treatment strategies for CKD-aP, which mainly include pharmacological treatment, non-pharmacological treatment and dialysis modality modification. This article mainly reviews recent advances in the pathogenesis and pharmacological treatment of pruritus among hemodialysis patients.

The risk factors of acute kidney injury caused by strenuous exercise include dehydration of the body, elevated body temperature, and intake of large amounts of sugary drinks after exercise, etc. The possible mechanism of the injury may be the inflammatory reaction of the body or the kidney itself, and the accumulation of various metabolites causing damage to the structure and function of the kidney under the induction of various risk factors. Repeated exposure to those risk factors not only increase the risk of acute kidney disease, but also may lead to chronic kidney disease. The paper reviews the definition, epidemiology, clinical manifestations, pathogenesis, and prevention measures of exercise-related kidney injury, to provide guidance for the formulation of appropriate exercise programs.

Patients with chronic kidney disease (CKD) are at high risk for suffering sarcopenia, but there is no unified criteria for diagnosing sarcopenia in CKD patients. It is well known that skeletal muscle mass and function are the key parameters to define sarcopenia based on the consensus published internationally. Recently, the need for the accuracy and applicability of assessment tools has facilitated the development of high-resolution imaging measurement and ultrasound evaluation. Sarcopenia in CKD is underrecognized in China resulting in clinical missed diagnosis and misdiagnosis prevalently. This article reviews the research progress of epidemiology, evaluation, prevention and treatment of sarcopenia in CKD patients.

Relapsing is the clinical characteristic of nephrotic syndrome (NS) in children, and some steroid-sensitive NS (SSNS) children have frequently relapsing NS and steroid-dependent NS. The long-term and frequent uses of glucocorticoids, as well as the adverse effects of immunosuppressants, seriously affect the quality of life in children with NS. The International Pediatric Nephrology Association released the clinical practice recommendation for SSNS in children in 2022. Based on the guideline for the diagnosis and treatment of steroid-sensitive, frequently- relapsing/dependent NS in children (2016) formulated by the Nephrology Group of Pediatrics Society of Chinese Medical Association, we interpreted the guideline on clinical treatment and management suggestions of SSNS, to provide references for the diagnosis and treatment of SSNS in children.

Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, which seriously affects the prognosis of patients. It is a series of abnormal mineral and bone metabolism syndrome caused by chronic renal function decline. The clinical manifestations are mainly decreased or increased serum calcium, increased serum phosphorus, increased intact parathyroid hormone, osteoporosis, and vascular calcification, etc. The paper reviews the research progress in the diagnosis, treatment and management based on the basic and clinical studies of hyperphosphatemia, secondary hyperparathyroidism, renal osteodystrophy and vascular calcification, etc.

Coronavirus disease 2019 (COVID-19) is a systemic disease including pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 infects several organs and systems besides the respiratory system, including the urinary system, cardiovascular system, gastrointestinal system, nervous system, hematological system and immune system. The kidney, as one of the targeted organs of COVID-19, is damaged by SARS-CoV-2 in both direct and indirect ways. The clinical manifestations of kidney involvements include acute kidney injury (AKI), proteinuria, hematuria, etc. Patients with chronic kidney disease (CKD) are often combined with a variety of immunodeficiency, especially those receiving hormones/immunosuppressants for immune nephropathy, kidney transplantation, undergoing renal replacement therapy for end-stage renal disease (ESRD). Moreover, these patients are not only susceptible to SARS-CoV-2, but also prone to becoming seriously or critically ill after infection. The treatment of CKD patients with COVID-19 is different from that of non-CKD patients, and the use of antiviral drugs in patients with severe renal insufficiency remains controversial. Furthermore, CKD patients are often combined with malnutrition, hypercoagulability, chronic inflammation, and water-electrolyte disorders, which make treatment of COVID-19 difficult. Therefore, this expert consensus was developed to enhance the clinicians' awareness of CKD with COVID-19, standardize the clinical diagnosis and treatment, and further improve the prognosis of patients.

Objective To explore the expression of type 2 complement receptor (CR2) in mesangial cells of the renal tissue in IgA nephropathy (IgAN) and its possible mechanism involved in complement C3 deposition. Methods The demographic data, samples of plasma and renal tissues of primary IgAN patients diagnosed by renal biopsy in the Guangdong Provincial People's Hospital from August 2021 to May 2022 were collected. According to the fluorescent intensity of mesangial complement C3 deposition, the patients were divided into complement C3 deposition ≥2+ group and complement C3 deposition <2+ group. The circulating IgA and complement C3 levels were detected by enzyme linked immunosorbent assay (ELISA). The influencing factors of kidney prognosis, plasma IgA and complement C3 levels were compared between the two groups. Immunofluorescence was used to detect the expression of IgA, complement C3 and CR2 in the renal mesangial cells of IgAN patients and normal renal tissues around renal carcinoma. Human mesangial cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was incubated with IgA protein (2 g/L) for 8 hours. The expressions of CR2 protein and mRNA were measured by Western blotting and real-time fluorescence quantitative PCR. The biological function of differential genes was analyzed by gene ontology (GO) and Kyto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results A total of 75 patients with IgAN were included in this study, including 50 patients in the complement C3 deposition ≥2+ group and 25 patients in the complement C3 deposition <2+ group. The proportions of patients with urine red blood cell count negative, 1+, 2+ and 3+-4+ in the complement C3 deposition ≥2+ group were 2.0%, 8.0%, 18.0% 72.0%, respectively, which were more serious than those in the complement C3 deposition <2+ group (4.0%, 4.0%, 52.0%, 40.0%) (Z=-2.320, P=0.020). Meanwhile, the proportion of S1 in Oxford pathological classification in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group (68.0% vs. 40.0%, χ²=5.389, P=0.020), and there were no statistically significant differences in gender, age, 24-hour urinary protein, serum creatinine, other indicators of Oxford pathological classification between the two groups. ELISA results showed that plasma IgA concentration in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group [3.62 (2.95, 5.53) g/L vs. 2.72 (2.15, 4.24) g/L, Z=2.405, P=0.016], and the plasma complement C3 concentration was lower than that in the complement C3 deposition <2+ group [199.6 (116.0, 328.0) mg/L vs. 319.2 (158.3, 454.5) mg/L, Z=-2.383, P=0.017]. Spearman correlation analysis showed that the complement C3 deposition intensity was positively correlated with IgA deposition intensity in mesangial area (r_s=0.441, P<0.001). Immunofluorescence results showed that there was colocalization of IgA and complement C3 in the glomeruli of IgAN patients. The expression of CR2 in the kidney was consistent with complement C3 deposition, and CR2 was colocalization with complement C3. In vitro experiments, the expression of CR2 in IgA protein group was higher than that in the control group (P<0.05). GO and KEGG enrichment analysis found that IgA protein induced active changes in various pathways of mesangial cells. Conclusion IgA protein induces mesangial cells to express CR2 and participates in complement C3 deposition, which may be an important mechanism of complement C3 activation in IgAN.

Alport syndrome (AS), also known as "eye-ear-kidney syndrome or hereditary nephritis", is a common hereditary disorder. AS is caused by pathogenic mutations of type Ⅳ collagen genes (COL4α3, COL4α4 and COL4α5), leading to defects in the basement membrane of glomeruli, cochlea, and ocular lens. Patients present with hematuria, proteinuria, and progressive renal failure. With the redefinition of AS and the clinical application of high-throughput sequencing technology, the prevalence of AS may be much higher than the previously recognized. The specific pathogenic mechanism of AS is unknown. Recent studies have showed that type Ⅳ collagen gene mutation may lead to kidney injury by causing abnormal basement membrane components, lipid deposition, energy metabolism disorders, endoplasmic reticulum stress, inflammation and fibrosis. Renin-angiotensin system inhibitor is the main therapy of AS, but the effect is not satisfactory. The new therapeutic strategies mainly include inhibition of abnormal collagen signal transduction, reduction of endoplasmic reticulum stress in podocytes, regulation of energy metabolism, antioxidant stress, anti-inflammation and fibrosis, gene and stem cell therapy. The paper reviewed the research progress on pathogenesis and new therapies of AS.

Osteoporosis is a comorbidity or complication of chronic kidney disease (CKD). Low bone mineral density, osteoporosis, and fractures are risk factors of poor prognosis in patients with CKD. Active prevention and treatment of osteoporosis is essential for patients with CKD. Denosumab is a fully human monoclonal antibody that targets receptor activator of nuclear factor-κB ligand (RANKL) and is not metabolized or excreted by the kidney. Clinical studies have shown that the use of denosumab in CKD (including dialysis and renal transplantation) patients with osteoporosis, can increase bone mineral density and reduce the incidence of fractures with acceptable safety. As hypocalcemia has been observed in patients with CKD, close monitoring and early supplementation of calcium and vitamin D are required before denosumab initiation, and serum calcium levels need to be monitored during treatment. The review summarized the published literature of denosumab in bone protection of CKD.

Objective To explore the relationship between the levels of serum complement C3 and C4 and the degree of renal pathological injury in patients with IgA nephropathy (IgAN). Methods It was a retrospective study. The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology of the Second People's Hospital of Qujing City, Yunnan Province from December 1, 2019 to December 31, 2022 were collected. According to the IgAN Oxford classification criteria, the patients were divided into mild renal pathological injury group (mild group, <3 pathologic types) and severe renal pathological injury group (severe group, ≥3 pathological types). The levels of serum C3 and C4 and other clinical data were compared between the two groups. Spearman correlation method was used to analyze the correlation between serum C3, C4 levels and estimated glomerular filtration rate (eGFR) during renal biopsy.Multivariate logistic regression model was used to analyze the influencing factors of the pathological injury degree in IgAN patients and the forest map depicted the effect of risk factors. Results A total of 164 IgAN patients were included in the study, including 77 males (47.0%), aged (35.5±12.9) years old. There were 60 patients in the mild group and 104 patients in the severe group. Compared with the mild group, the patients in the severe group were older, had higher levels of serum C4, serum uric acid, low density lipoprotein cholesterol and 24 h urinary protein, higher proportions of hypertension, glucocorticoids/immunosuppressant therapy, C3 deposition in renal tissues and microscopic hematuria, and had lower hemoglobin and serum C3 level (all P<0.05). The results of Spearman correlation analysis showed that the level of serum C3 was positively correlated with eGFR (r=0.303, P<0.001), and the level of serum C4 was negatively correlated with eGFR (r=-0.238, P=0.002). Multivariate logistic regression analysis results showed that serum C3 (every 0.01 g/L increase, OR=0.976, 95% CI 0.957-0.996, P=0.018), serum C4 (every 0.01 g/L increase, OR=1.091, 95% CI 1.020-1.166, P=0.011), hemoglobin (OR=0.969, 95% CI 0.950-0.988, P=0.002), and serum uric acid (OR=1.005, 95% CI 1.001-1.009, P=0.012) were independent related factors of renal pathological damage (severe injury /mild injury) in IgAN patients. Conclusions Serum C3 and C4 are independent related factors of the severity of renal pathological injury in IgAN patients.

It was a retrospective study. The patients with type 2 diabetes mellitus (T2DM) who underwent renal biopsy in the Department of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2021 were enrolled to analyze the pathological and clinical manifestations of kidney. There were 483 patients enrolled, including 136 patients who had no history of diabetes mellitus, newly diagnosed as T2DM according to an oral glucose tolerance test. The age was (52.80±13.13) years old. There were 337 males (69.77%). Based on the renal biopsy, the patients were classified as diabetic kidney disease (DKD, 22.15%, 107/483), DKD+non-diabetic kidney disease (NDKD)(6.63%, 32/483), and NDKD (71.22%, 344/483). Membranous nephropathy was the most common pathology in patients with NDKD (40.41%, 139/344) and DKD+NDKD (34.38%, 11/32). In the 136 newly diagnosed T2DM patients, there were 3 patients (2.21%) with DKD, 2 patients (1.47%) with DKD+NDKD, and 131 patients with NDKD (96.32%). The proportions of DKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 10.53% (6/57), 25.00% (16/64), 26.53% (26/98), 41.56% (32/77) and 47.06% (24/51), respectively. The proportions of DKD+NDKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 3.51% (2/57), 3.13% (2/64), 10.20% (10/98), 9.09% (7/77) and 17.65% (9/51), respectively. Multivariate logistic regression analysis results showed that, the duration of diabetes history (OR=1.130, 95% CI 1.057-1.208, P<0.001), diabetes retinopathy (OR=12.185, 95% CI 5.331-27.849, P<0.001), urinary red blood cell count (OR=0.987, 95% CI 0.974-0.999, P=0.039), glycosylated hemoglobin (OR=1.482, 95% CI 1.119-1.961, P=0.006) as well as hemoglobin (OR=0.973, 95% CI 0.957-0.990, P=0.001) were independently correlated with DKD. The proportions of DKD and DKD+NDKD increase with the prolongation of diabetes history. Membranous nephropathy is the most common pathology in NDKD and DKD+NDKD patients. Even in patients newly diagnosed with T2DM, it is necessary to screen for DKD. The duration of diabetes history, diabetes retinopathy, urinary red blood cell count, glycosylated hemoglobin and hemoglobin may be used to identify DKD from NDKD.

Renal fibrosis (RF) is the key pathological feature for the progression of chronic kidney disease to end-stage renal failure. It has been an important scientific issue to understand its mechanism of RF in the field of kidney diseases in the past near two centuries. The progress of science and technology has not only provided a strong tool for RF research, but also given us many new ideas for RF prevention and treatment. The paper briefly reviews the key histories of RF research, with focuses on early studies of renal fibrosis, application of renal biopsy technology, establishment of RF animal models, advancements in cell and molecular biotechnology, and exploration into mechanisms underlying RF, to clarify future directions for chronic kidney disease prevention and treatment research.

As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Objective To investigate the urinary sediment findings and the clinicopathologic features of IgA nephropathy (IgAN) patients with acute kidney injury (AKI). Methods It was a retrospective study. The patients with renal biopsy-proven primary IgAN in Peking University First Hospital from January 31, 2013 to July 31, 2015 were selected. According to whether AKI occurred at renal biopsy or not, the patients were divided into AKI group and non-AKI group. Morning urine samples were obtained on the day of renal biopsy. Urine sediments, including various cells and casts, were examined. The clinical data, urinary sediments, and renal pathological changes were compared between the two groups. Logistic regression analysis was performed to identify the association between clinical pathological changes, urinary sediment indicators and AKI, or clinical pathological changes and urinary sediment indicators. Results There were 502 IgAN patients enrolled in this study, with age of (36.1±12.1) years old and 261 males (52.0%). The incidence of AKI was 11.4% (57/502) among the enrolled patients at the time of renal biopsy. Common causes of AKI included gross hematuria-induced AKI (10 cases), acute tubulointerstitial nephritis (10 cases), crescentic IgAN (9 cases), malignant hypertensive renal damage (6 cases), and multiple etioloqy or unknown etiology (22 cases). Compared with non-AKI group, AKI group had higher proportions of males and malignant hypertension, higher levels of proteinuria and urinary erythrocyte counts, and higher frequencies of gross hematuria, leukocyturia, renal tubular epithelial cells, and granular casts (all P<0.05). AKI group also had higher proportions of severe tubular atrophy/interstitial fibrosis (T2) and cellular/cellular fibrous crescent formation (C2) than non-AKI group (both P<0.05). Logistic regression analysis results showed that, there were statistically significant differences in the correlation between AKI and gender, 24 h urinary protein, urinary erythrocyte counts, granular casts and renal tubular atrophy/interstitial fibrosis (T) scores (all P<0.05). Hematuria, leukocyturia, red blood cell casts, white blood cell casts, granular casts, and fatty casts were correlated with endothelial hypercellularity (E) and cellular/cellular fibrous crescent formation (C) scores, respectively (all P<0.05). Hematuria was correlated with mesangial hypercellularity (M) scores (OR=2.613, 95% CI 1.520-4.493, P=0.001). Hematuria (OR=1.723, 95% CI 1.017-2.919, P=0.043) and fatty casts (OR=2.646, 95% CI 1.122-6.238, P=0.026) were correlated with segmental sclerosis or adhesion (S) scores. Leukocyturia (OR=1.645, 95% CI 1.154-2.347, P=0.006) and fatty casts (OR=2.344, 95% CI 1.202-4.572, P=0.012) were correlated with T scores. Epithelial cell cast was correlated with C scores (OR=1.857, 95% CI 1.174-2.939, P=0.008). Conclusions AKI is a common complication among IgAN patients with diverse etiology and more severe clinicopathological features. Urinary sediment findings can reflect renal pathological changes to some extent, and therefore assist in the clinical diagnosis and treatment of IgAN patients with AKI.

Objective To explore the clinical value of N terminal pro B type natriuretic peptide (NT-proBNP) in diagnosing or predicting heart failure in peridialysis chronic kidney disease (CKD) population. Methods It was a single-center retrospective study. Patients with peridialysis CKD who visited the Department of Nephrology, First Affiliated Hospital of Zhengzhou University from January 2021 to June 2021 were collected and divided into 4 groups according to the presence or absence of heart failure and the level of left ventricular ejection fraction (LVEF), namely the non-heart failure group, heart failure with reduced ejection fraction (HFrEF) group (LVEF<40%), heart failure with mid-range ejection fraction (HFmrEF) group (40％≤LVEF<50％), and heart failure with preserved ejection fraction (HFpEF) group (LVEF≥50％). The NT-proBNP, echocardiography and other indicators of the 4 groups were compared. The value of plasma NT-proBNP in diagnosing heart failure, HFpEF, HFmrEF and HFrEF was analyzed by drawing receiver operating characteristic curve (ROC curve). Logistic regression analysis was used to analyze the related factors of heart failure in peridialysis CKD patients. Results A total of 508 patients were included, including 11 cases in the HFrEF group, 29 cases in the HFmrEF group, 152 cases in the HFpEF group, and 316 cases without heart failure. The differences in age, 24-h urine volume, hemodialysis proportion, non-dialysis proportion, serum creatinine, estimated glomerular filtration rate, hemoglobin, serum albumin, C-reactive protein, NT-proBNP, cardiac troponin I, left ventricular internal diameter, LVEF, pulmonary artery systolic pressure, left ventricular end-diastolic volume, E/A value, septal thickness, and left ventricular posterior wall thickness among the four groups were statistically significant (P < 0.05, respectively). A two-pair comparison (all P values corrected by Bonferroni method) revealed that the 24-h urine volume was higher in the non-heart failure group than in the other three groups (corrected P<0.05, respectively), while the proportion of hemodialysis patients and the levels of NT-proBNP and C-reactive protein were lower in the non-heart failure group than in the other three groups (corrected P<0.001, respectively); the levels of hemoglobin and serum albumin were lower in the HFpEF group than in the non-heart failure group (corrected P<0.001, respectively); troponin I was lower in the non-heart failure group than in the HFpEF group (corrected P<0.001), HFmrEF group (corrected P=0.001) and HFrEF group (corrected P<0.001), and troponin I was lower in the HFpEF group than in the HFrEF group (corrected P=0.008); LVEF was higher in the non-heart failure group than in the other three groups (corrected P<0.001, respectively), and LVEF in the HFpEF group was higher than in the HFmrEF and HFrEF groups (corrected P<0.001, respectively). For patients with peridialysis CKD, the cut-off values of plasma NT-proBNP for diagnosing or predicting heart failure, HFpEF, HFmrEF and HFrEF were 4 943.33 ng/L, 4 976.83 ng/L, 14 964.5 ng/L and 17 847.55 ng/L, respectively. Multivariate logistic regression analysis showed that NT-proBNP (every 500 ng/L increase, OR=1.390, 95% CI 1.287-1.501, P<0.001), LVEF (OR=0.747, 95% CI 0.656-0.851, P<0.001) and 24-h urine volume (every 100 ml increase, OR=0.842, 95% CI 0.763-0.929, P=0.001) were independently correlated with heart failure. Conclusions The cut-off value of plasma NT-proBNP for diagnosing or predicting heart failure in peridialysis CKD patients is much higher than that in patients with normal renal function. NT-proBNP, LVEF and 24-h urine volume are independently associated with heart failure in peridialysis CKD patients.

Objective To explore the risk factors of poor renal prognosis in patients with coronary artery bypass surgery (CABG)-associated acute kidney injury (AKI), and establish a preliminary clinical risk prediction model for chronic kidney disease (CKD) progression in CABG-associated AKI patients, and evaluate its predictive efficacy. Methods It was a retrospective, observational cohort study. The study subjects were patients who underwent CABG at Central China Fuwai Hospital from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min^-1·(1.73 m²)^-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD after 90 days of the occurrence of CABG-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint events. The baseline clinical data were compared between the two groups. The logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic curve was drawn to evaluate the performance of the clinical risk prediction model for predicting poor renal prognosis in CABG-associated AKI patients. Results A total of 124 CABG-associated AKI patients were enrolled in the study, including 95 males and 29 females, aged (62.57±9.61) years old. Thirty-eight patients (30.8%) progressed to new-onset CKD 90 days after CABG-associated AKI. Compared with non-CKD group, CKD group had lower preoperative hemoglobin (t=2.778, P=0.006) and baseline eGFR (t=3.603, P<0.001), higher proportion of women (χ²=10.714, P=0.001), and higher preoperative blood NT-proBNP (Z=-2.150, P=0.030) and discharged serum creatinine (Z=-5.290, P<0.001). The multivariate logistic regression analysis results revealed that female (OR=5.179, 95% CI 1.535-17.477, P=0.008), high preoperative blood NT-proBNP (OR=1.049, 95% CI 1.004-1.095, P=0.032), low baseline eGFR (OR=0.928, 95% CI 0.889-0.968, P=0.001), and high serum creatinine at discharge (OR=1.019, 95% CI 1.009-1.029, P<0.001) were independent influencing factors of CABG-associated AKI to CKD. The clinical risk prediction model including female, preoperative blood NT-proBNP, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting CABG-associated AKI to CKD (AUC=0.872, 95% CI 0.806-0.939, P<0.001). Conclusion Patients with CABG-associated AKI are at high risks for new-onset CKD. Female, preoperative high NT-proBNP, preoperative low baseline eGFR and high serum creatinine at discharge can help identify patients with a high risk of CABG-associated AKI to CKD.

Objective To establish a conditional knockout mouse model of polycystic kidney disease 1 (Pkd1) gene based on CRISPR/Cas9 and Cre-loxP gene editing technology, and to provide an animal model for in-depth research on the role of Pkd1 gene in the development of polycystic kidney disease. Methods In-Fusion technology was used to construct a targeting vector. Corresponding gRNAs, Cas9 mRNAs, and donor vectors carrying the loxP site were prepared based on the Pkd1 gene, and injected into the fertilized eggs of C57BL/6N mice. The fertilized eggs were transferred to the fallopian tubes of female mice with pseudopregnancy. After the newborn mice were identified by PCR and sequencing analysis, Pkd1^flox/flox F0 generation positive mice were selected. The F0 generation positive mice were bred with wild-type mice, and F1 generation heterozygous mice with Pkd1^flox/+ genotype were selected for offspring. F2 generation homozygous mice with Pkd1^flox/flox genotype were obtained through internal expansion, and then hybridized with Cre positive Ggt1/Cre mice. F3 generation mice with Pkd1^{flox/+Ggt1Cre} genotype were obtained. F4 generation mice with Pkd1^flox/flox Ggt1^Cre genotype were obtained by self crossing or backcrossing with F2 generation Pkd1^flox/flox, namely kidney-specific Pkd1 gene knockout mice (Ggt1-cKO mice). PCR method was used to identify the genotype of mice, and then the mice were divided into wild-type control (WT) group (n=6), Pkd1 homozygous control (PKD) group (n=6), and Ggt1-cKO knockout validation (CKO) group (n=6) according to the gene identification results. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of Pkd1 mRNA in the kidneys and other organs of mice in each group. HE staining was used to detect the pathological changes in renal tissues of mice in each group. The automatic biochemical detector was used to detect the blood urea nitrogen and serum creatinine levels of mice, and the kidney coefficient was calculated. Results The PCR detection results showed that the genotype of offspring mice in CKO group was consistent with Pkd1^{floxflox Ggt1Cre . Pkd1 gene was only specifically expressed in the kidney, but not in other tissues. The RT-qPCR results showed that the relative expression of Pkd1 mRNA in the renal medulla of CKO group was significantly lower than that of WT and PKD groups. The kidney volume of the CKO group had increased by about twice compared to the WT group. Under the microscope, it could be observed that there were multiple vacuoles of varying sizes and shapes in the kidneys of the CKO group, and there was a significant increase in the interstitial space of the medullary tissue. The kidney coefficient, blood urea nitrogen, and serum creatinine in the CKO group were significantly higher than those in the WT and PKD groups (all P<0.05). Conclusion Based on CRISPR/Cas9 and Cre-loxP gene editing technology, Pkd1 gene kidney conditional knockout mice can be successfully constructed, providing an animal model for further studying the action mechanism of Pkd1 gene in polycystic kidney disease.}

Objective To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 (NR4A1) in suppressing cisplatin nephrotoxicity. Methods The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 (NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells (P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. 2023 International Society for Peritoneal Dialysis (ISPD) catheter-related infection recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection, such as cause-specific catheter-related infection, culture-negative catheter-related infection, refractory catheter-related infection, and infection- related catheter removal. A new target for the exit site infection rate should not exceed 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations for exit site infection include clarified suggestion of exit site dressing cover and revised topical antibacterial agents as well as antibiotics treatment duration. In addition to catheter removal and reinsertion, new salvage options for catheter are suggested. The paper outlines the updated main content of the guide.

The article reported one case of renal damage caused by lenvatinib in the treatment of advanced primary liver cancer. The patient was a 63-year-old male who was admitted to the hospital due to "liver cancer for 4 years, blood pressure elevation for nearly 2 years, and edema for 7 months". During the treatment of liver tumors with atezolizumab combined with lenvatinib, blood pressure increased and renal insufficiency aggravated progressively. Pathological light microscopy of renal biopsy showed endothelial cell lesion and tubulointerstitial damage, and electron microscopy showed moderate proliferation of mesangial cells and deposition of mesangial matrix. There were many agglomerated low-electron density deposits in the mesangial area, and a small amount of electron dense deposits in the subendothelium. The pathological diagnosis was endothelial cell disease (thrombotic microangiopathy) and secondary focal segmental glomerulosclerosis. Renal injury was considered as secondary to lenvatinib. After discontinuing lenvatinib and giving angiotensin receptor antagonist treatment, blood pressure was normal, urine protein turned negative, and renal function improved significantly after 8 months of outpatient follow-up.

Objective To investigate the association between body mass index (BMI) and waist circumference (WC) with all-cause mortality in middle-aged and elderly patients receiving maintenance hemodialysis (MHD). Methods It was a prospective cohort study. The clinical data of MHD patients aged ≥50 years old from eleven hemodialysis centers from April to June 2017 in Beijing were analyzed. The patients were divided into low BMI group [body mass index (BMI)<18.5 kg/m²], normal BMI group (18.5 kg/m²≤BMI <24.0 kg/m²), overweight group (24.0 kg/m²≤BMI<28.0 kg/m²) and obesity group (BMI≥28.0 kg/m²) by BMI, and central obesity group (male ≥85 cm, female ≥80 cm) and normal WC group (male <85 cm, female <80 cm) by WC. Kaplan-Meier survival analysis method was used to compare the difference of all-cause mortality between those groups. Multivariate Cox regression model was used to analyze the association of BMI and WC with all-cause mortality. Results A total of 613 MHD patients were enrolled, with age of (63.82±7.14) years old and 258 (42.09%) females. There were 46 (7.50%) patients in the low BMI group, 303 (49.43%) patients in the normal BMI group, 227 (37.03%) patients in the overweight group and 37 (6.04%) patients in the obesity group. In addition, 346 (56.44%) patients were categorized as central obesity. Kaplan-Meier survival analysis results showed that the all-cause mortality rates of low BMI group (log-rank χ²=13.571, P<0.001) and obesity group (log-rank χ²=6.664 P=0.010) were higher than that of normal BMI group, and the all-cause mortality rate of central obesity group was higher than that of normal WC group (log-rank χ²=5.698, P=0.017). Multivariate Cox regression analysis results showed that， besides the low BMI group and obesity group (with normal BMI group as a reference, HR=5.289, 95% CI 2.318-12.067, P<0.001; HR=5.360, 95% CI 2.088-13.760, P<0.001, respectively), normal BMI and overweight combined with central obesity were also independently correlated with all-cause mortality (with normal WC group as a reference, HR=2.605, 95% CI 1.199-5.663, P=0.016; HR=1.787, 95% CI 1.026-3.732, P=0.031, respectively). Conclusions Lower and higher BMI or combined central obesity are independently associated with all-cause mortality in the middle-aged and elderly patients receiving MHD.

Objective To determine the impact of early serum sodium concentrations on the survival prognosis in maintenance hemodialysis (MHD) patients. Methods It was a retrospective cohort study. The newly admitted hemodialysis patients who were included in the registration system of Zhejiang Province Dialysis Quality Control Center from January 1, 2010 to December 31, 2019 were identified. Follow-up was conducted until December 31, 2020. Baseline data were collected for the first three months of dialysis, in which the mean level of serum sodium was defined as early serum sodium. Patients were divided into five groups based on early serum sodium level. Restricted cubic spline (RCS) was used to fit the relationship between long-term serum sodium level and risk of death. Kaplan-Meier model and Log-rank test were used to compare the survival rates of different groups. Multivariable Cox regression was used to analyze the correlation between early serum sodium level and death. Results A total of 26 309 MHD patients were included in this study, and their ages were (59.07±15.41) years (ranging from 18 to 100 years). Among them, 13 643 (51.9%) were over 60 years old and 15 843 (60.2%) were males. Among the primary diseases of chronic renal failure, chronic glomerulonephritis was the first [13 703 cases (52.1%)], followed by diabetic nephropathy [6 460 cases (24.6%)], hypertensive nephropathy [1 293 cases (4.9%)], polycystic kidney disease [1 164 cases (4.4%)], etc. According to early serum sodium level, 12 883 patients (49.0%) had hyponatremia (serum sodium <135 mmol/L), of which 4 001 patients (15.2%) had serum sodium ≤130 mmol/L; 1 529 patients (5.8%) had hypernatremia (serum sodium >145 mmol/L). Patients were divided into the following 5 groups: 4 001 cases (15.2%) in group 1 (serum sodium ≤130 mmol/L), 8 882 cases (33.8%) in group 2 (130 <serum sodium <135 mmol/L), 8 231 cases (31.3%) in group 3 (135≤serum sodium ≤140 mmol/L), 3 666 cases (13.9%) in group 4 (140 < serum sodium≤145 mmol/L) and 1 529 cases (5.8%) in group 5 (>145 mmol/L). Among them, patients in the Na≤130 mmol/L group had a slightly older age, a higher proportion of diabetes and cardiovascular disease, a lower level of blood uric acid, albumin, hemoglobin, and a higher level of alkaline phosphatase and leukocytes, while patients in the Na >145 mmol/L group had an older age and a higher proportion of cardiovascular disease. After follow-up of (55.67±33.58) months, a total of 4 954 patients (18.8%) died, 1 537 patients (5.8%) underwent kidney transplantation, 128 patients (0.5%) were converted to peritoneal dialysis. Of the deaths, 990 (20.0%) were due to cardiovascular diseases, 498 (10.1%) to cerebrovascular diseases and 400 (8.1%) to infections, and cardiovascular disease was the main cause of death. RCS curve fitting of the relationship between serum sodium level and risk of death found that the all-cause mortality hazard ratio (HR) increased with decreasing or increasing serum sodium, and the optimal serum sodium was between 135 mmol/L and 140 mmol/L. Kaplan-Meier survival curve showed that the risk of all-cause death (Log-rank test, χ²=66.5, P<0.001), the risk of cardiovascular death (Log-rank test, χ²=31.5, P<0.001) and the risk of infection death (Log-rank test, χ² =28.6, P<0.001) were significantly different among five groups. The 10-year cumulative survival rate was 63.0%, 71.5%, 72.5%, 67.8% and 61.4% in groups with different serum sodium levels from low to high, and the 10-year cumulative cardiovascular mortality rate was 9.6%, 6.2%, 5.5%, 7.3% and 11.7%, and the 10-year cumulative infection mortality rate was 4.9%, 3.2%, 1.7%, 2.8% and 3.9%. Multivariable Cox regression showed early serum sodium level >145 mmol/L was an independent relevant factor for all-cause death in MHD patients (HR=1.237, 95% CI 1.045-1.465, P=0.013). Conclusions MDH patients are more likely to develop hyponatremia in the early stage of dialysis. The cumulative survival rate of all-cause death, cardiovascular death and infection death in patients with predialysis serum sodium ≤130 mmol/L and >145 mmol/L within three months after initiation of dialysis is significantly lower than those in other levels. Early serum sodium >145 mmol/L is associated with higher mortality in MHD patients.

Objective To investigate the impacts of hierarchical management based on medical alliance on the patency of arteriovenous graft (AVG),and provide a basis for further exploration of optimal AVG management. Methods In this retrospective cohort study, clinical and follow-up data of patients with AVG established in the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2021 were analyzed. Patients were divided into medical alliance group and non-medical alliance group according to whether they were under hierarchical management model, and the patency rate of AVGs and the incidence of clinical events were compared between the two groups. Results A total of 328 AVGs were included in this study, which were from 151 hemodialysis centers, including 189 AVGs (57.6%) from 72 centers in medical alliance group, and 139 AVGs (42.4%) from 79 centers in non-medical alliance group. The age of the patients was (55.57±11.80) years, among whom 130 (39.6%) were males and 126 (38.4%) were diabetic. The follow-up time of AVGs in this cohort was 15.5 (9.5, 26.2) months, with 15.4 (9.8, 25.2) months in medical alliance group and 15.5 (9.2, 27.3) months in non-medical alliance group. The incidence of thrombosis or occlusion (0.328 times/patient-year), graft dissection (0.007 times/patient-year), graft infection (0.030 times/patient-year), and catheter utilization (0.043 times/patient-year) in the medical alliance group were lower than those in the non-medical alliance group (0.589 times/patient-year, 0.040 times/patient-year, 0.054 times/patient-year and 0.147 times/patient-year, respectively), and there was no significant difference in clinic follow-up rates between the two group (1.91 times/patient-year vs. 1.94 times/patient-year). The median primary patency time was 17.4 (95% CI 11.3-23.5) months, the median primary assisted patency time was 32.6 (95% CI 25.0-40.2) months, and the median secondary patency time was 47.9 (95% CI 40.0-55.8) months in the medical alliance group, compared with 12.3 (95% CI 9.4-15.2) months, 19.4 (95% CI 14.3-24.5) months, and 34.6 (95% CI 29.3-39.9) months in the non-medical alliance group, respectively. Primary patency were significantly higher in the medical alliance group (77.4%, 62.2%, 39.9%, and 26.6%) than those in the non-medical alliance group (71.1%, 50.1%, 30.6%, and 13.4%) at 6, 12, 24, and 36 months (Log-rank test, χ²=4.504, P=0.034). Primary assisted patency were significantly higher in the medical alliance group (90.9%, 84.3%, 67.1%, and 46.1%) than those in the non-medical alliance group (89.2%, 75.7%, 42.0%, and 16.6%) at 6, 12, 24, and 36 months (Log-rank test, χ²=10.655, P=0.001). Secondary patency were significantly higher in the medical alliance group (96.8%, 91.8%, 84.2%, and 74.0%) than those in the non-medical alliance group (89.9%, 85.8%, 69.3%, and 47.5%) at 6, 12, 24, and 36 months (Log-rank test, χ²=11.634, P=0.001). Multivariate Cox regression analysis showed that it was a protective factor for primary patency (HR=0.708, 95% CI 0.512-0.980, P=0.037), primary assisted patency (HR=0.506, 95% CI 0.342-0.749, P=0.001) and secondary patency (HR=0.432, 95% CI 0.261-0.716, P=0.001) under the medical alliance model. Conclusion The hierarchical management based on medical alliances can improve the patency of AVGs and reduce the incidence of clinical events.

Targeted therapy and immunotherapy have achieved great success in treating various solid and non-solid tumors, but the incidence of drugs-related adverse events is relatively high. The paper reports a case of renal thrombotic microangiopathy in an intrahepatic cholangiocarcinoma patient who underwent targeted therapy combined with immunotherapy. During the treatment, the tumor burden relieved continuously, but the patient developed proteinuria, edema and hypertension. The ADAMTS13 activity and inhibitors were normal, while the antiphospholipid antibody was positive. The patient was finally diagnosed as glomerular thrombotic microangiopathy with immune complex deposition by renal biopsy. After the cease of the antineoplastic agents and treatment with "cordyceps preparations" and "α-keto acids", the patient's blood pressure dropped to normal, her urine protein turnned to weakly positive, and her renal function remained stable.

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.

Objective To investigate the changes of podocyte circadian rhythm in the high-glucose environment and diabetic nephropathy (DN) mouse model and the protective effect of melatonin on podocyte injury in DN. Methods Primary podocytes were cultured in vitro and divided into 3 groups: control group, high glucose (30 mmol/L) group and high glucose (30 mmol/L) treated with melatonin (0.1 mmol/L or 0.5 mmol/L) group. The podocytes were collected every 4 hours for 24 hours, synchronized with dexamethasone (100 nmol/L) for 2 hours, which was recorded as zeitgeber time 0 point. Male C57BL/6J mice aged 6-8 weeks and weighing about 20 g were randomly (randomized block) assigned to three groups: control group, DN (high-fat diet+streptozotocin 120 mg/kg intravenously injected) group, and DN (high-fat diet+streptozotocin 120 mg/kg intravenously) treated with melatonin (20 mg/kg intragastric treatment) group (melatonin group). Real-time quantitative PCR was used to detect the mRNA levels of rhythm genes in podocytes. Western blotting was used to detect the protein expression levels of circadian clock genes (Clock and Bmal1), podocyte marker proteins (Nephrin, Synaptopodin, WT1, and Desmin) and autophagy-related proteins (Beclin1, LC3Ⅱ/Ⅰ and P62). Immunofluorescence staining was used to detect the protein expression level of WT1, and immunohistochemistry was used to analyze the protein expression levels of P62 and cleaved-caspase-3 in renal tissues of mice. The pathological changes of renal glomerulus were observed under electron microscope. Results (1) Dexamethasone reseted the expression and rhythmic oscillation of circadian clock genes in podocytes. The circadian rhythmic oscillations of Clock and Ck1e mRNA in the high glucose group were flattened compared to the control group, and the circadian rhythmic oscillations in Clock and Ck1e mRNA expression were partial recovery in high glucose treated with melatonin group (all P<0.05). (2) Compared with the control group, the protein expression levels of Nephrin, Synaptopodin and WT1 were lower while Desmin was higher in the high glucose group (all P<0.05). The protein expression levels of Nephrin, Synaptopodin and WT1 were higher and the protein expression level of Desmin was lower in the high glucose treated with melatonin (0.5 mmol/L) group compared with the high glucose group (all P<0.05). (3) The invivo experimental results showed that compared with the DN group, melatonin group had higher protein expression levels of glomerular Nephrin and WT1, and lower urinary albumin/creatinine ratio, width of foot process and thickness of glomerular basement membrane (all P<0.05). The protein expression levels of Beclin1 and LC3Ⅱ/Ⅰ in the DN group were lower than those in the control group, and the protein expression level of P62 was higher than that in the control group (all P<0.05). Compared with the DN group, the protein expression levels of Beclin1 and LC3Ⅱ/Ⅰ in the melatonin group were significantly higher, and the protein expression level of P62 was lower (all P<0.05). Conclusions Melatonin can partially restore the circadian rhythm of clock genes in high-glucose environment, improve autophagy and alleviate injury in podocytes.

Objective To screen the incidence of proteinuria in rural areas of Shanxi province and construct a risk prediction model of proteinuria based on machine learning algorithm. Methods It was a cross-sectional investigation study. The residents ≥30 years old in rural areas of Shanxi province from April to November 2019 were screened by multi-stage stratified sampling method, and data from questionnaire surveys, physical examinations, and laboratory examinations were collected. Urine albumin/creatinine ratio ≥30 mg/g was defined as proteinuria, and the incidence of proteinuria was calculated. Subjects were divided into proteinuria group and non-proteinuria group. The machine learning binary classification model of proteinuria and non-proteinuria was constructed based on the stackable integrated logistic regression algorithm (SE-LR), logistic regression, support vector machine, decision tree, random forest and extreme gradient lift algorithms, respectively. The area under the receiver operating characteristic curve, accuracy, recall, and F1 weights were used to evaluate the predictive efficiency of the comparison models. Finally, the importance of the predictive features of the model with the best overall performance was ranked. Results There were 8 869 rural residents included in the study, aged (58.59±9.49) years old, with 3 872 males (43.66%) and 4 997 females (56.34%). The prevalence of proteinuria in rural areas of Shanxi province was 13.49% (1 196/8 869). Blood pressure, pulse, body mass index, waist circumference, proportion of obesity or overweight, proportion of hypertension, proportion of moderate to severe salt intake, glycosylated hemoglobin, uric pH value, urinary specific gravity, proportion of positive urinary occult blood, proportion of positive urinary glucose, proportion of positive urinary ketone body, proportion of urinary red blood cell count ≥5/μl, proportion of urinary white blood cell count ≥10/μl and urinary α1 microglobulin in the proteinuria group were all higher than those in the non-proteinuria group (all P<0.05). The proportions of lack of exercise and drinking history in the proteinuria group were lower than those in non-proteinuria group (both P<0.05). The overall performance of SE-LR model was the best, with the area under the curve (0.736, 95% CI 0.719-0.746) slightly lower than that of the logistic regression model (0.745, 95% CI 0.680-0.762), and the highest accuracy (0.844), recall rate (0.621) and F1 weighting value (0.801). In the SE-LR model, the orders of importance of the top 10 features were urinary α1- microglobulin, urinary occult blood, urinary sugar, uric acid basicity, smoking history,overweight or obesity, body mass index, total cholesterol, glycosylated hemoglobin and hypertension. Conclusions The prevalence of proteinuria is high in rural areas of Shanxi province. The risk prediction model of proteinuria established by machine learning algorithm can predict the risk of proteinuria and identify its risk factors, which can provide a scientific basis for disease prevention, intervention, and treatment in the community and clinic to a certain extent.

Objective To investigate the correlation between serum anti-phospholipase A2 receptor antibody (SAb) combined with glomerular complement C3 (GC3) deposition and clinicopathologic features and prognosis in patients with idiopathic membranous nephropathy (IMN). Methods It was a retrospective cohort study. The patients diagnosed with IMN in Affiliated Hospital of Qingdao University from July 1, 2019 to April 30, 2022 were enrolled, and the clinical and pathological data were collected and analyzed. The patients were divided into negative SAb and negative GC3 (SAb^-/GC3^-) group, negative SAb and positive GC3 (SAb^-/GC3⁺) group, positive SAb and negative GC3 (SAb⁺/GC3^-) group and positive SAb and positive GC3 (SAb⁺/GC3⁺) group according to the status of SAb titer and GC3 deposition. Clinical and pathological characteristics among the groups were compared. Kaplan-Meier survival curve was used to compare the cumulative renal remission rates of different groups. Cox regression analysis model was used to analyze the related factors of renal remission. Results A total of 143 IMN patients aged (53.35±12.34) years old were included in the study, including 94 males (65.7%). There were 17 patients (11.9%) in the SAb^-/GC3^- group, 30 patients (21.0%) in the SAb^-/GC3⁺ group, 19 patients (13.3%) in the SAb⁺/GC3^- group, and 77 patients (53.8%) in the SAb⁺/GC3⁺ group. Compared with SAb^-/GC3^- group, the level of serum albumin was lower in the SAb⁺/GC3⁺ group, and the level of 24 h urine protein, SAb titer, and the proportions of glomerular anti-phospholipase A2 receptor antigen and renal tubule atrophy were higher in the SAb⁺/GC3⁺ group (all P<0.05). After 26.0 (19.0, 36.0) months of follow-up, a total of 96 patients (67.1%) attained remission. The proportion of patients receiving immunosuppressive therapy in the SAb⁺/GC3⁺ group was higher than that in the SAb^-/GC3^- group [93.5% (72/77) vs. 70.6% (12/17), fisher value=8.974, P=0.016] and the proportion of renal remission rate in the SAb⁺/GC3⁺ group was lower than that in the SAb^-/GC3^- group [49.4% (38/77) vs. 100% (17/17), χ²=25.438, P<0.001]. Kaplan-Meier survival curve result showed that the cumulative renal remission rate in the SAb⁺/GC3⁺ group was significantly lower than that in the SAb^-/GC3^- group (Log-rank χ²=31.538, P<0.01). Multivariate Cox regression analysis result showed that 24 h urine protein level (HR=0.891, 95% CI 0.803-0.988, P=0.029), SAb titer (HR=0.996, 95% CI 0.992-1.000, P=0.042) and SAb⁺/GC3⁺ (with SAb^-/GC3^- group as reference, HR=0.414, 95% CI 0.204-0.827, P=0.013) were independent related factors for renal remission in patients with IMN. Conclusions IMN patients with positive SAb and GC3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rates, and are more likely to have poor prognosis. The combined assessment of SAb and GC3 deposition may be helpful for evaluating prognosis and guiding treatment in IMN patients.

In recent years, artificial intelligence has received extensive attention in the field of kidney pathology, such as identifying kidney tissue structure and evaluating the degree of lesions. Renal pathology is the gold standard for the diagnosis of renal diseases, and histochemistry staining is the prerequisite for the assessment of renal lesions. Renal biopsy is usually evaluated by various staining methods, including hematoxylin-eosin staining, periodic acid-Schiff reaction, Masson's trichrome staining and immunol staining, among that, different staining methods focus on different structures. The paper reviewed the application and progress of artificial intelligence in renal pathology, especially in different staining methods.