Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Clinical features of acute kidney injury in patients with nephrotic syndrome and minimal change disease: a retrospective, cross-sectional study / 中华医学杂志(英文版)

BACKGROUND@#Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome.@*METHODS@#Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis.@*RESULTS@#A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P < 0.001). The percentage of AKI increased with age in the MCD patients. The percentage of AKI in patients aged 50 years or older was 52.9% (46/87), which was significantly higher than that [22.5% (63/280)] in patients under 50 years (χ2 = 6.347, P = 0.013). We observed statistically significant differences in age (43 [27, 59] years vs. 28 [20, 44] years, Z = 5.487, P < 0.001), male (78.0% vs. 51.4%, χ2 = 22.470, P < 0.001), serum albumin (19.9 ± 6.1 g/L vs. 21.5 ± 5.7 g/L, t = 2.376, P = 0.018), serum creatinine (129.5 [105.7, 171.1] μmol/L vs. 69.7 [57.7, 81.9] μmol/L, Z = 14.190, P < 0.001), serum urea (10.1 [6.2, 15.8] mmol/L vs. 4.7 [3.6, 6.4] mmol/L, Z = 10.545, P < 0.001), IgE (266.0 [86.7, 963.0] IU/ml vs. 142.0 [35.3, 516.5] IU/ml, Z = 2.742, P = 0.007), history of diabetes (6.4% vs. 1.2%, P = 0.009), and history of hypertension (23.9% vs. 5.1%, χ2 = 28.238, P < 0.001) between the AKI group and the non-AKI group. According to multivariate linear regression analysis, among the renal pathological features analyzed, renal tubular epithelial cell damage (β = 178.010, 95% CI: 147.888-208.132, P < 0.001) and renal interstitial edema (β = 28.833, 95% CI: 11.966-45.700, P = 0.001) correlated with serum creatinine values.@*CONCLUSIONS@#The percentage of AKI in MCD patients is significantly higher than that in MN patients. Patients over 50 years old are more likely to develop AKI. Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study / 中国结合医学杂志

OBJECTIVE@#To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction.@*METHODS@#Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period.@*RESULTS@#After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year.@*CONCLUSION@#Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Progress of small ubiquitin-related modifiers in kidney diseases / 中华医学杂志(英文版)

OBJECTIVE@#Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases.@*DATA SOURCES@#This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases."@*STUDY SELECTION@#Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English.@*RESULTS@#SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome.@*CONCLUSIONS@#Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.

Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians / 中华医学杂志(英文版)

BACKGROUND@#Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy.@*METHODS@#A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis.@*RESULTS@#The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001).@*CONCLUSIONS@#The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.

A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity / 中华医学杂志(英文版)

BACKGROUND@#Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN.@*METHODS@#A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model.@*RESULTS@#There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P < 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of I, II, III, IV, and V accounted for 2.21%, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade III being the most prevalent. The levels of urea nitrogen (UN) (13.57 ± 5.95 vs. 6.06 ± 3.63, 5.92 ± 2.97, 5.41 ± 1.73, and 8.41 ± 3.72 mmol/L, respectively) and creatinine (Cr) (292.19 ± 162.21 vs. 80.42 ± 24.75, 103.79 ± 72.72, 96.41 ± 33.79, and 163.04 ± 47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45 ± 7.56, 67.16 ± 6.94, 63.22 ± 8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB) (2.34 ± 1.23, 2.58 ± 1.40, 1.91 ± 0.97, and 1.81 ± 1.44 vs. 0.74 ± 0.57 μmol/L, respectively), and IgA (310.35 ± 103.78, 318.48 ± 107.54, 292.58 ± 81.85, and 323.29 ± 181.67 vs. 227.17 ± 68.12 g/L, respectively) were significantly increased in grades II-V compared with grade I (all P < 0.05).@*CONCLUSIONS@#The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.

Prevention and treatment of combat injury and acute renal injury related to special working environment / 解放军医学杂志

[Abstract] Acute kidney injury (AKI) is a rapid decline in renal function caused by various etiologies, and is a common critical disease in combat and special working environment. The combat injury and special working environment-related AKI have the characteristics of high incidence and mortality, and the long-term prognosis of survival patients is poor. The present paper introduces the etiology, pathogenesis and main classification of AKI related to combat injury and special working environment, and expounds the present situation of early diagnosis and treatment of AKI and the existing problems. At present, the basic research on AKI is deepening, and the application of new diagnostic markers and renal replacement therapy equipment are becoming more and more active. In order to meet the treatment needs of AKI related to combat injury and special working environment in the future, this paper puts forward the corresponding prevention and treatment strategies, and looks forward to the development trend in this field in the future.

Clinicopathological Features of Nondiabetic Renal Diseases from Different Age Groups: An Observational Cross-sectional Study / 中华医学杂志(英文版)

Background@#Diabetes mellitus (DM) has become the leading cause of chronic kidney disease (CKD). Nondiabetic renal diseases (NDRDs) have different clinicopathological features and prognosis from those of diabetic nephropathy. Our study sought to analyze the clinical and pathological features of NDRDs, in different age groups through a cross-sectional study.@*Methods@#All patients with type 2 DM at our center who underwent renal biopsy between March 1997 and March 2017 were screened and divided into three groups by age: Group 1 (youth group), 18-44 years old; Group 2 (middle-aged group), 45-59 years old; and Group 3 (elderly group), ≥60 years old. We analyzed the clinicopathological data and risk factors by univariate and multivariate logistic regression for NDRD of the patients to identify the features of NDRD in different age groups.@*Results@#We included 982 patients in the final analysis. Patients with NDRD accounted for 64.4% of all patients. IgA nephropathy (IgAN) was the most common pathological pattern in young patients with NDRD, accounting for 26.3%. In the middle-aged group, the two most common pathological patterns were IgAN and membranous nephropathy. Membranous nephropathy was the most common pathological pattern in elderly patients with NDRD, accounting for 29.3%. Consistent with pathological features, glomerular hematuria is a risk factor for NDRD in Group 1 (odds ratio [OR], 26.514; 95% confidence interval [CI], 2.503-280.910; P = 0.006). On the other hand, rapidly increasing proteinuria or nephrotic syndrome is a risk factor for NDRD in Group 2 (OR, 5.921; 95% CI, 2.061-17.013; P = 0.001) and Group 3 (OR, 90.409; 95% CI, 6.198-1318.826; P = 0.001).@*Conclusions@#This single-center study showed that the proportion and composition of NDRD differ among different age groups. Consistent with pathological features, some clinical indices such as hematuria and proteinuria showed different features among different age groups.

New Mutation of Coenzyme Q Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient / 中华医学杂志(英文版)

Background@#Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism.@*Methods@#Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX.@*Results@#Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group.@*Conclusions@#This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

Infection is Associated with Occurrence of Proteinuria in Type 2 Diabetes Patients: A Systemic Review and Meta-Analysis / 中华医学杂志(英文版)

Background@#Type 2 diabetes (T2DM) patients are susceptible to Helicobacter pylori (HP), and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients; however, this view remains controversial. This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients. In addition, we hope to provide some recommendations to readers in clinical or related fields.@*Methods@#Our meta-analysis was conducted with the methodology of the Cochrane Collaboration. Search strategies were formulated by relevant professionals. Case-control studies that compared the occurrence of proteinuria in T2DM patients with and without HP infection were involved in our meta-analysis. Relevant English or Chinese studies were searched on online databases before 2018, including PubMed, the Cochrane library, Medline, Google Scholar, the China National Infrastructure, and Wanfang database. The search strategies were "diabetic proteinuria, diabetic microalbuminuria, diabetic albuminuria, diabetic kidney disease, diabetic renal dysfunction, diabetic renal disease, diabetic nephropathy, diabetic complications, and diabetic mellitus, combined with HP." The quality of these involved articles was separately assessed by two investigators using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) and associated 95% confidence intervals (CIs) were extracted and pooled using fixed-effects models.@*Results@#Seven studies involving 1029 participants were included. The quality of these seven articles was all above five stars as assessed by NOS, and there was no significant publication bias in our meta-analysis. We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR: 2.00, 95% CI: 1.48-2.69).@*Conclusions@#Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients. HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.

Potential Value ofAgglutinin-recognized Glycopatterns in Urinary Protein on Differential Diagnosis of Diabetic Nephropathy and Nondiabetic Renal Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetic nephropathy (DN) is the most common and serious microvascular complication of diabetes. To date, the gold standard for identifying DN and nondiabetic renal disease (NDRD) is a renal biopsy; however, there is currently no reliable diagnostic marker to identify DN and NDRD in a noninvasive manner. This study aimed to investigate the different glycopatterns in urine specimens of DN patients and NDRD patients for a differential diagnosis.</p><p><b>METHODS</b>In total, 19 DN patients and 18 NDRD patients who underwent renal biopsies between March 2015 and March 2016 at the Chinese People's Liberation Army General Hospital were enrolled in this study. A lectin microarray was used to investigate the glycopatterns in the urinary protein of the 37 patients. Ratio analysis and one-way analysis of variance were used to screen altered glycopatterns. Then, the altered glycopatterns between the DN and NDRD groups were verified by a urinary protein microarray among another 32 patients (15 with DN and 17 with NDRD), and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of the altered glycopatterns in differentiating DN and NDRD. Finally, lectin blotting was used to evaluate the altered glycosylation in protein level.</p><p><b>RESULTS</b>The result of lectin microarrays revealed that the relative abundance of the (β-1,4)-linked N-acetyl-D-glucosamine (GlcNAc) recognized by lectin Datura stramonium agglutinin (DSA) was significantly higher in urinary protein in DN patients than that in NDRD patients (fold change >1.50, P < 0.001). Subsequently, the results of urinary protein microarrays were consistent with lectin microarrays (P < 0.05). Furthermore, the ROC curve showed that glycopatterns could effectively distinguish DN from NDRD patients (area under the ROC curve = 0.94, P < 0.001). DSA lectin blotting showed that glycoproteins, with a molecular weight of approximately 50,000, demonstrated a difference in urine samples between DN patients and NDRD patients.</p><p><b>CONCLUSIONS</b>The relative abundance of (β-1,4)-linked GlcNAc recognized by lectin DSA and urinary glycoprotein with a molecular weight of approximately 50,000 are significantly different between DN and NDRD patients, indicating that the glycopatterns could be used as potential biomarkers for a differential diagnosis.</p>

Safety, Effectiveness, and Manipulability of Peritoneal Dialysis Machines Made in China: A Randomized, Crossover, Multicenter Clinical Study / 中华医学杂志(英文版)

Background@#Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared.@*Methods@#Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups.@*Results@#The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition.@*Conclusions@#The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability.@*Trial Registration@#Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.

Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients: A Multicenter Study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.</p><p><b>METHODS</b>Participants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.</p><p><b>RESULTS</b>In total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.</p><p><b>CONCLUSIONS</b>Hemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.</p>

Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD.</p><p><b>METHODS</b>Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining.</p><p><b>RESULTS</b>In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs.</p><p><b>CONCLUSIONS</b>In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.</p>

Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.</p><p><b>METHODS</b>It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.</p><p><b>RESULTS</b>The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.</p><p><b>CONCLUSIONS</b>Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.</p><p><b>TRIAL REGISTRATION</b>chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.</p>

Efficacy and safety of Flos Abelmoschus manihot (Malvaceae) on type 2 diabetic nephropathy: A systematic review / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Flos Abelmoschus manihot (Malvaceae) on type 2 diabetic nephropathy (DN).</p><p><b>METHODS</b>The Cochrane Library, PubMed/MEDLINE, Excerpta Medical Database, Chinese electronic literature databases, and the references of relevant articles were searched in March 2012 for randomized controlled trials (RCTs) that reported the effects of Flos A. manihot on type 2 DN patients with overt but subnephrotic-range proteinuria (500-3,500 mg/24 h). The quality of trials was evaluated using the Cochrane-recommended method. The results were summarized as risk ratios (RRs) for dichotomous outcomes or mean differences (MDs) for continuous outcomes.</p><p><b>RESULTS</b>Seven trials (531 patients) were included. Flos A. manihot significantly decreased proteinuria [MD -317.32 mg/24 h, 95% confidence interval (CI) [-470.48, -164.17],P<0.01]. After excluding a trial that only included patients with well-preserved renal function, Flos A. manihot was associated with a significant decrease in serum creatinine (MD -11.99 μmol/L, 95% CI [-16.95, -7.04],P<0.01). Serious adverse events were not observed. The most common adverse event was mild to moderate gastrointestinal discomfort; however, patients receiving this herb did not have an increased risk for tolerated gastrointestinal discomfort (RR 1.48, 95% CI [0.39, 5.68],P=0.57).</p><p><b>CONCLUSIONS</b>Flos A. manihot may be considered as an important adjunctive therapy with the first-line and indispensable therapeutic strategies for type 2 DN. High-quality RCTs are urgently needed to confirm the effect of Flos A. manihot on definite endpoints such as end-stage renal disease.</p>

Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.</p><p><b>METHODS</b>Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.</p><p><b>RESULTS</b>Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.</p><p><b>CONCLUSIONS</b>The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.</p>

Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.</p><p><b>METHODS</b>The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.</p><p><b>RESULTS</b>The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).</p><p><b>CONCLUSIONS</b>The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.</p>

Expressions of gelatinases in diffuse proliferative lupus nephritis and its clinical significance / 中华风湿病学杂志

Objective To investigate the roles and significances of MMP-2 and MMP-9 in diffuse proliferative lupus nephritis by repeated renal biopsy.Methods Seventeen patients diagnosed by renal biopsy as WHO typeⅣlupus nephritis were analyzed by immunohistochemistry staining for MMP-2 and MMP-9. Double staining for MMP-2 and MT1-MMP,MMP-9 and CD68 were also performed.Patients had repeated renal biopsy after followed up for 2.5 years.The relationship between expressions of gelatinases and pathological activity index and clinical data were studied.Results MMP-2 immunoreactivity was detected in normal controls and was increased in diffuse proliferative lupus nephritis.MMP-9 staining,which was almost negative in normal giomeruli,was increased much more significantly in diffuse proliferative lupus nephritis. The immunoreactivity of MMP-2 and MMP-9 was positive in MT1-MMP staining and CD68-positive macrophages, respectively.The expression of MMP-2 and MMP-9 was reduced by 70% and 62% in 10 patients whose clinical condition was partially alleviated,while the expressions in 7 patients whose clinical condition was not alleviated,were only reduced by 27% and 32%.The staining for MMP-2 and MMP-9 were correlated with activity index of lupus nephritis and proteinuria.Conclusion Up-regulation of gelatinases expression in diffuse proliferate lupus nephritis is correlated to activity index of the disease.

Inflammatory reaction changes with aging in kidneys of human TIMP-1 transgenic mice / 中华老年医学杂志

Objective To explore the role of tissue inhibitor of metalloproteinase-1(TIMP-1) during renal senescence by using human TIMP-1 transgenic mice.Methods Renal histological changes of wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-schiff(PAS)staining of paraffin sections.The numbers of F4/80 positive cells were detected by immunofluoreseence.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,intercellular adhesion molecule-1(ICAM-1),transforming growth factor?1(TGF-?1),collagenⅢand collagenⅣwere detected by Western blot.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results Focal renal fibrosis was found in two genotypes with aging.At the age of 24 months,compared with wild type,in kidneys of transgenic type,the expressions and activities of gelatinases were dowregulated (MMP-2:2.08?0.20 vs.3.39?0.43;MMP-9:4.02?0.82 vs.6.72?1.40,all P＜0.05);the expressions of collagenⅢ,collagenⅣ,ICAM-1,and TGF-?1 were upragulated(0.72+0.11 vs.0.57?0.09;0.84?0.13 vs.0.6?0.11,0.72?0.12 vs.0.53?0.07; 0.69?0.12 vs.0.45?0.09,all P＜0.05),and the numbers of F4/80 positive cells were increased (18.8?4.4 vs.12.7?3.6,P＜0.05)with the upregulated expression and activity of TIMP-1(1.10?0.18 vs.0.62?0.09;50.75?7.25 vs.20.64?3.50,P＜0.05).Conclusions TIMP-1 could promote age-related renal fibrosis through enhancing inflammation reaction by ICAM-1 upregulation.