Advances in the treatment of IgA nephropathy with biological agents.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease, and the "four-hit" theory represents its currently accepted pathogenic mechanism. Mucosal immunity triggered by infections in the respiratory tract, intestines, or other areas leads to antigen presentation, T cell stimulation, B cell maturation, and the production of IgA-producing plasma cells. The proteins B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are involved in this process, and alternative complement and lectin pathway activation are also part of the pathogenic mechanism. Kidney Disease Improving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking, with renin-angiotensin-aldosterone system inhibitors being the primary therapy. Recent research shows that biological agents can significantly reduce proteinuria, stabilize the estimated glomerular filtration rate, and reverse some pathological changes, such as endocapillary proliferation and crescent formation. There are four main categories of biological agents used to treat IgA nephropathy, specifically anti-CD20 monoclonal antibodies, anti-BLyS or APRIL monoclonal antibodies, monoclonal antibodies targeting both BLyS and APRIL (telitacicept and atacicept), and monoclonal antibodies inhibiting complement system activation (narsoplimab and eculizumab). However, further research on the dosages, treatment duration, long-term efficacy, and safety of these biological agents is required.

Urine albumin-to-creatinine ratio diurnal variation rate predicts outcomes in idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease (ESRD). The purpose of this study was to evaluate whether urinary albumin-to-creatinine ratio (UACR) diurnal variation rate calculated by spot urinary protein test predicts 1-year nephrotic outcomes as a biomarker of proteinuria severity in patients with IMN. METHODS: Patients' baseline demographics, blood and urinary biomarkers, and clinical and pathological characteristics were collected retrospectively. Urine samples were collected at 7:00 (before breakfast) and 19:00 (after dinner) to calculate the UACR diurnal variation rate. A prediction model for no remission (NR) was developed statistically based on differences between prognosis groups. Receiver operating characteristic curve (ROC) analysis was performed to evaluate prediction abilities and determine optimal cut-off points of the model and UACR diurnal variation rate alone. RESULTS: The formula for calculating the probability of NR was exp(L)/(1 + exp(L)), where the linear predictor L = - 22.038 + 0.134 × Age (years) + 0.457 × 24-h urinary protein + 0.511 × blood urea nitrogen (BUN) + 0.014 × serum uric acid (SUA) + 2.411 if glomerular sclerosis + 0.816 × fasting blood glucose (FBG)-0.039 × UACR diurnal variation rate (%). Optimal cut-off points for NR prediction by the final model and UACR diurnal variation rate alone were 0.331 and 58.5%, respectively. Sensitivity and specificity were 0.889 and 0.859 for the final model, and 0.926 and 0.676 for UACR diurnal variation rate alone. CONCLUSION: UACR diurnal variation using spot urinary protein is a simpler way to predict nephrotic outcomes and is a highly sensitive screening tool for identifying patients who should undergo further comprehensive risk assessment.

Clinicopathologic features and long-term prognosis of hepatitis B virus-associated glomerulonephritis: a retrospective cohort study.

BACKGROUND: Hepatitis B virus-associated glomerulonephritis is a common form of secondary glomerulonephritis in China. However, the clinicopathological features and long-term prognosis of Hepatitis B virus-associated Glomerulonephritis remain only partially known. METHODS: Biopsy-proven Hepatitis B virus-associated Glomerulonephritis patients were enrolled between November 1994 and December 2013 at our center. The composite endpoints were doubling serum creatinine, end-stage renal disease, or death from renal disease during follow-up. The clinicopathological features and predictors of the long-term prognosis of Hepatitis B virus-associated Glomerulonephritis patients were explored. RESULTS: The median age of the 259 Hepatitis B virus-associated Glomerulonephritis patients was 31.0 years (IQR 24.0-40.0), and 71.0% were males. Among the patients, 45.2% presented with nephrotic syndrome, and 45.9% presented with proteinuria combined with hematuria. The two most prevalent pathological patterns were IgA nephropathy (27.0%) and membranous nephropathy (27.0%). The mean follow-up period was 68.8 ± 46.9 months. The 3-, 5-, and 10-year clinical event-free survival rates were 93.4%, 85.2%, and 70.3%, respectively. Multivariable Cox regression analysis showed that hypertension (HR 2.580, 95% CI 1.351-4.927, P = 0.004), hyperuricemia (HR 2.101, 95% CI 1.116-3.954, P = 0.021), glomerulosclerosis (P = 0.001), and intrarenal arterial lesions (P = 0.041) were independent predictors of composite clinical event endpoint. Patients in the antiviral therapy group exhibited a significantly better prognosis compared to those who received no antiviral therapy (log-rank χ2 = 5.772, P = 0.016). CONCLUSION: Hepatitis B virus-associated Glomerulonephritis has specific clinicopathologic features and should not be considered a benign disease in adults. Hypertension, hyperuricemia, glomerulosclerosis, and intrarenal arterial lesions were independent predictors of the long-term prognosis in Hepatitis B virus-associated Glomerulonephritis patients. Antiviral therapy could be effective in improving the long-term prognosis of Hepatitis B virus-associated Glomerulonephritis patients.

Obesity-Related Glomerulopathy: From Mechanism to Therapeutic Target.

Obesity-related glomerulopathy (ORG) is a secondary glomerular disease caused by obesity, with clinical manifestations such as proteinuria and glomerulomegaly. Currently, the high incidence of obesity brings a change in the spectrum of kidney diseases across the globe, including China. ORG has become another important secondary nephropathy leading to end-stage renal disease (ESRD), and its incidence has increased significantly. This trend is bound to bring about a serious socioeconomic burden. Therefore, it is urgent to study its pathogenesis and intervention measures. Currently, the occurrence and development mechanisms in ORG are complicated by many factors, which are still unclear. In the past 20 years, with the continuous intensive research on mechanisms such as hypoxia in the metabolic process, immune inflammation, and pyroptosis, there have been new advances in the mechanism of ORG, especially the important role of inflammation in podocyte injury and its impact on the progress of ORG. Here, we briefly review the possible pathogenic role of the inflammasome in the podocyte damage in ORG and summarize the possible therapeutical strategies targeting inflammasome.

Severity of Intrarenal Arterial Lesions Can Predict the Clinical Prognosis of Hepatitis B Virus-Associated Glomerulonephritis: A Retrospective Study.

BACKGROUND: Intrarenal arterial lesions (IALs) have been studied in immunoglobulin A nephropathy and lupus nephritis, but this has not been reported in hepatitis B virus-associated glomerulonephritis (HBV-GN). This study aims to investigate the prevalence and the role of IALs in HBV-GN. METHODS: IALs were examined in kidney biopsy specimens from 205 patients with HBV-GN retrospectively. The severity of IALs and tubular interstitial lesions was scored semi-quantitatively. The severity of IALs was divided into 4 groups on the basis of ILA score, which were no IALs (Score 0), mild IALs (Score 1-2), moderate IALs (Score 3-4), and severe IALs (Score 5-10) groups. Survival analysis was performed using the Kaplan-Meier method between the severity of IALs and clinical events (doubling of serum creatinine [SCr], ESRD, and death due to the kidney disease). RESULTS: Among 205 patients with HBV-GN, 143 (69.8%) had IALs in their kidney biopsy specimens. IALs were mild in 28 (19.6%) patients, moderate in 101 (70.6%) patients, and severe in 14 (9.8%) patients. The severity of IALs was associated with high blood pressure (BP), high SCr, and severe tubulointerstitial injuries. The average follow-up time of these 205 HBV-GN patients was 94.2 ± 47.1 months, in which 46 cases had clinical event. The proportions of clinical events in no IAL, mild IAL, moderate IAL, and severe IAL groups were 9.7, 14.3, 25.7, and 71.4%, respectively. Event-free survival of patient in IAL group was significantly lower than that in the no IAL group (p = 0.000). Multivariate cox regression analysis indicated SCr (1.011, 1.007-1.016), hypertension (1.767, 1.004-3.108), and IAL (2.194, 1.062-4.530) were independent risk factors for clinical events after adjustment for age and gender. Event-free clinical survival in moderate and severe IAL groups was significantly lower than that in the no IAL group (p = 0.0111 and p = 0.0001, respectively). Besides, event-free renal survival in severe IAL group was significantly lower than that in moderate IAL group (p = 0.009). Multivariate cox regression analysis showed that the more severe the IALs, the higher the risk of the clinical event, with a hazard ratio of 2.284 for moderate IALs (1.085-4.907) and 3.315 for severe IALs (1.296-8.482). CONCLUSIONS: Severity of IALs is associated with high BP, reduced renal function, and poor clinical prognosis in HBV-GN patients.

Executive Summary: Clinical Practice Guideline for Autosomal Dominant Polycystic Kidney Disease in China.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, with a prevalence of 1/2,500-1/1,000, and it affects 1.25 million people in China. ADPKD is responsible for nearly 5% of end-stage renal disease cases, which leads to a major burden on public health. In 2016, the Chinese working group developed guidelines for the diagnosis and treatment of ADPKD, which promoted the clinical management of ADPKD in China. In the last 3 years, Chinese clinicians have deepened their understanding and standardized the management of ADPKD, and several basic and clinical studies on ADPKD have been conducted. In combination with international guidelines and research results, the working group updated the ADPKD guidelines in China. This guideline includes 5 chapters: introduction, diagnosis, kidney disease progression monitoring, treatment, and family planning. We highlight the main recommendations and suggestions of the ADPKD guidelines in this summary.

Study on hyperuricemia in HBV-associated glomerulonephritis.

OBJECTIVES: To determine the prevalence and risk factors for hyperuricemia in hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: Univariate and multivariate logistic regression analysis was applied to decide the risk factors of hyperuricemia in HBV-GN, and clinical and pathologic data were compared between HBV-GN patients with hyperuricemia and those with normal serum uric acid. RESULTS: Among our 227 HBV-GN cases, 31.3% of the patients had hyperuricemia at the time of renal biopsy. Univariate analysis showed that the level of serum creatinine and the severity of glomerular and tubular interstitial injury were significantly related to hyperuricemia. Multivariate logistic regression analysis identified the levels of serum creatinine and tubular interstitial injury as independent factors for hyperuricemia. The incidence of hypertension and lower estimated glomerular filtration rate was significantly higher in hyperuricemic patients with HBV-GN than in normouricemic patients. There were also fewer membranous nephropathy, more proliferative sclerosing glomerulonephritis, and more tubular interstitial injury in hyperuricemic patients with HBV-GN. CONCLUSIONS: Our study results suggest that hyperuricemia is common in HBV-GN, which may facilitate the progression of HBV-GN and renal tubular interstitial injury as well as the development of hypertension.

Novel fluoropolymer anion exchange membranes for alkaline direct methanol fuel cells.

A series of novel fluoropolymer anion exchange membranes based on the copolymer of vinylbenzyl chloride, butyl methacrylate, and hexafluorobutyl methacrylate has been prepared. Fourier transform infrared (FT-IR) spectroscopy and elemental analysis techniques are used to study the chemical structure and chemical composition of the membranes. The water uptake, ion-exchange capacity (IEC), conductivity, methanol permeability, and chemical stability of the membranes are also determined. The membranes exhibit high anionic conductivity in deionized water at 65 °C ranging from 3.86×10(-2) S cm(-1) to 4.36×10(-2) S cm(-1). The methanol permeability coefficients of the membranes are in the range of 4.21-5.80×10(-8) cm(2) s(-1) at 65 °C. The novel membranes also show good chemical and thermal stability. An open-circuit voltage of 0.7 V and a maximum power density of 53.2 mW cm(-2) of alkaline direct methanol fuel cell (ADMFC) with the membrane C, 1 M methanol, 1 M NaOH, and humidified oxygen are achieved at 65 °C. Therefore, these membranes have great potential for applications in fuel cell systems.

[The expression and significance of nephrin in hepatitis B virus-associated membranous nephropathy].

OBJECTIVE: To observe the expression of nephrin in hepatitis B virus-associated membranous nephropathy (HBV-MN), and investigate the impairment and significance of podocyte in HBV-MN. METHODS: The protein expression of nephrin in renal biopsy specimens in 35 patients, who were diagnosed as HBV-MN by renal biopsy, was determined by immunohistochemistry and tested by semi-quantitative method. The relationship between the expression of nephrin and clinicopathological data was analyzed. RESULTS: Among the 35 cases with HBV-MN, 6 were in MN phase I, 20 in MN phase II and 9 in MN phase III. A strong intensity expression of nephrin in normal glomerulus was found along capillary loop of glomerulus, while its expression in HBV-MN patients decreased obviously. There was no significantly difference in the expression of nephrin among the different stages of HBV-MN (P > 0.05). The expression of nephrin in different clinical types was significantly different(P < 0.05). The expression of nephrin in patients with nephrotic syndrome was significantly lower than that in patients without nephrotic syndrome (P < 0.01). The expression of nephrin in different grades of 24-hour urinary protein excretion quantity was significantly different(P < 0.05). There was negative correlation between the expression of nephrin and 24-hour urinary protein excretion quantity(r = -0.378, P < 0.05). In the patients with HBV-MN phase II, the expression of nephrin in patients with nephrotic syndrome was also significantly lower than that in patients without nephrotic syndrome (P < 0.01). CONCLUSIONS: The damage of podocytes emerge in the early stage of HBV-MN and the expression of nephrin in HBV-MN patients, especially in patients with nephrotic syndrome, are significantly down regulated. The descended expression of nephrin in HBV-MN patients may promote the production of proteinuria.

Association of metabolic syndrome and IgA nephropathy.

BACKGROUND: The disorders associated with metabolic syndrome (MS) can lead to renal disease. IgA nephropathy is the most common form of glomerulonephritis, and many patients with this disorder progress to renal failure. AIMS: To identify the effect of MS on IgA nephropathy by retrospectively comparing patients who had IgA nephropathy and MS with those who had IgA nephropathy alone. METHODS: 30 patients with MS and IgA nephropathy (MS group), and 30 matched controls with IgA nephropathy alone (non-MS group) were enrolled. IgA nephropathy was diagnosed by renal biopsy; activity and severity was graded by two classification systems. MS was diagnosed by criteria of the Diabetes Society of the Chinese Medical Association. RESULTS: Simple and multiple linear regression models (which adjusted for age, gender and body surface area) showed that only hypertension significantly affected serum creatinine, an indicator of the clinical severity of renal disease. Simple and multiple linear regression models (which adjusted for age, gender and body surface area) also showed that hypertensive patients had higher Katafuchi scores, an indicator of the pathological severity of renal disease. CONCLUSION: Among the disorders associated with MS, hypertension is the most important factor for renal disease.

[Study on the relationship between blood stasis syndrome and clinical pathology in patients with IgA nephropathy].

OBJECTIVE: To explore the relationship between blood stasis Syndrome and clinical pathological parameters in patients with IgA nephropathy (IgAN). METHODS: The clinicopathological data were analyzed of 94 IgAN patients of traditional Chinese medicine blood stasis syndrome. RESULTS: Of the 94 IgAN patients, 61.70% had blood stasis syndrome (BS) and 38.30% had non- blood stasis syndrome (non-BS). In patients with BS, dark purple tongue proper was the symptom most commonly seen; the clinical manifestations were mostly proteinuria with hematuria, often accompanied with hypertension and renal dysfunction. Compared with those in patients without BS, plasma levels of serum creatinine (SCr), triglyceride (TG) and plasma fibrinogen (FIB) were obviously higher, activated partial thromboplastin time (APTT), and urokinase-type plasminogen activators (u-PA) significantly lower; and scores of glomerular sclerosis, tubular interstitial lesions, interstitial inflammatory cell infiltration, interstitial fibrosis, tubular atrophy and vascular sclerosis significantly higher. Besides, the Lee's grades in them of III - V were mostly seen. CONCLUSION: Blood stasis syndrome of IgAN are correlated with certain clinical parameters and severity of renal pathological changes. The combination of TCM holistic syndrome differentiation and modern medicinal micro-differentiation is more favorable for making clear the nature of blood stasis Syndrome of IgAN.

[The effects of angiotensin-converting enzyme inhibitor on IgA nephropathy and the influencing factors].

OBJECTIVE To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) on IgA nephropathy(IgAN) and the factors influencing the therapeutic effects. METHODS 131 cases with IgAN diagnosed by renal biopsy were randomly divided into two groups: ACEI group (benazepril 10 mg/d) and non-ACEI group as control. The pathological changes in the kidney were analyzed using Lee SMK. RESULTS After 1 month treatment of ACEI, the levels of proteinuria and serum cholesterol decreased significantly, meanwhile those of serum albumin and total protein increased obviously in patients with IgAN(P < 0.05). The proteinuria level at the 3rd month after treatment was lower than that at the 1st month, but was same as that at the 18th month. While in the control group the proteinuria level increased and the clearance of creatinine decreased continuously during the observation (P < 0.05). The effects correlated positively with mesangial proliferation and negatively with course of the disease glomerular sclerosis in glomerulus and changes of small arterioles in the kidney. Normal blood pressare normal renal function I approximately II degree of Lee SMK I degee of interstitial changes minimal changes of small arterioles and mild glomerular sclerosis predicted better response to ACEI treatment than hypertension renal insufficiency V degree of Lee SMK IV degee of interstitial changes severe changes of small arterioles and massive glomerular sclerosis. CONCLUSIONS It is suggested that benezepril could definitely reduce the excretion of urinary protein and protect renal function of patients with IgAN and should be used as earlier as possible. Mesangial prolife ration glomerular sclerosis in glomerulus changes of small arterioles in kidney and course of the disease are the major influencing factors of ACEI treatment on IgAN.

[The development and clinical applications of automatic negative pressure gun for biopsy].

Using the new negative pressure biopsy technology, the automatic negative pressure gun and the specific puncture needle for the biopsy have been developed. Renal biopsies were conducted in 1136 cases, with the success rate being 99.9%, and 29 cases gross hematuria while the hepatic biopsies were conducted in 16 cases, mass biopsies in 3 cases with the success rates being 100% respectively. The biopsy gun has the advantages of easy manipulation, higher success rate and lower incidence of complications.