Common Primary Glomerular Disease Research Articles

JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA Nephropathy.

IgA nephropathy is the most common primary glomerular disease in the world. Marked by mesangial inflammation and proliferation, it generally leads to progressive kidney fibrosis. As the Janus kinase signal transducer and activator of transcription pathway has been implicated as an important mediator of diabetic kidney disease and FSGS, detailed investigation of this pathway in IgA nephropathy was undertaken to establish the basis for targeting this pathway across glomerular diseases. Well characterized patients with IgA nephropathy and controls were studied, allowing us to compare 77 patients with biopsy-proven IgA nephropathy with 45 healthy subjects. STAT phosphorylation was assessed in peripheral blood monocytes (PBMCs) by phosphoflow before and after cytokine stimulation. Kidney Janus kinase signal transducer and activator of transcription activity was studied by immunofluorescence and by transcriptomic studies. An STAT1 activity score was established using downstream transcriptional targets of pSTAT1 and associated with disease and clinical outcomes. We found PBMCs to have upregulated pSTAT production at baseline in patients with IgA nephropathy with a limited reserve to respond to cytokine stimulation compared with controls. Increased staining in glomerular mesangium and endothelium was seen for Jak-2 and pSTAT1 and in the tubulointerstitial for JAK2, pSTAT1, and pSTAT3. Activation of the Janus kinase signal transducer and activator of transcription pathway was further supported by increased pSTAT1 and pSTAT3 scores in glomerular and tubulointerstitial sections of the kidney (glomerular activation Z scores: 7.1 and 4.5, respectively; P values: <0.001 and <0.001, respectively). Clinically, phosphoflow results associated with proteinuria and kidney function, and STAT1 activation associated with proteinuria but was not associated with progression. Janus kinase signal transducer and activator of transcription signaling was activated in patients with IgA nephropathy compared with controls. There were altered responses in peripheral immune cells and increased message and activated proteins in the kidney. These changes variably related to proteinuria and kidney function.

Patterns in renal diseases diagnosed by kidney biopsy: A single-center experience.

BackgroundThe worldwide incidence of renal disease diagnosed by a kidney biopsy varies with age, race, sex, and region. Owing to a lack of studies and limited research resources for this disease in Korea, we investigated renal disease patterns by analyzing data from kidney biopsies performed over 13 years in a university-based teaching hospital in Korea.MethodsAmong 2,053 kidney biopsies performed from 2001 to 2013 at Kyungpook National University Hospital, 1,924 were retrospectively analyzed for histopathologic, demographic, and clinical data as well as laboratory results.ResultsAmong the 1,924 studied kidney biopsies, 1,078 were males (56.0%) and the mean age was 37.7 ± 16.5 years. Asymptomatic urinary abnormalities were the most common clinical manifestation (62.5%). Immunoglobulin A nephropathy (IgAN) was the most common primary glomerular disease (37.4%), followed by minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulonephritis and crescentic glomerulonephritis. Secondary glomerular diseases accounted for 10.3% of the total biopsies, with lupus nephritis being the most common (4.6%) followed by Henoch-Schönlein purpura nephritis and diabetic nephropathy. The most common cause of nephrotic syndrome was MCD (42.1%) followed by MN. Among patients seropositive for hepatitis B or C, IgAN (28.3% and 21.4%, respectively) was the most common cause.ConclusionIgAN and lupus nephritis were the most common primary and secondary glomerular diseases, respectively. Race, region, and practice patterns may affect renal disease patterns in different cohorts.

Prognostic value of the Oxford classification and the Oxford score in IgA nephropathy: A Tunisian study.

Immunoglobulin A nephropathy is the most common primary glomerular disease. The main challenge in this disease is the evaluation of prognostic factors for end-stage renal disease. The aim of our study was to describe the characteristics of immunoglobulin A nephropathy, to evaluate the histological data according to Oxford classification, and to identify factors associated with renal survival. This was a retrospective study, including adults with primary immunoglobulin A nephropathy. The study was conducted over a period of 10 years. Renal biopsies were scored according to Oxford classification. Oxford score, based on the sum of the different histological lesions of Oxford classification, was calculated for each patient. We included 50 patients with a gender ratio (male:female) of 2.8. The average age was 35.6 ± 10.6 years. Fifty-eight percent of the patients had hypertension (HTN). The median proteinuria was 1.9 g/day. The median of the glomerular filtration rate was 47.6 mL/min/1.73 m2. According to Oxford classification, mesangial proliferation, endocapillary proliferation, glomerulosclerosis, interstitial fibrosis, and/or tubular atrophy and crescents were present in 40%, 38%, 88%, 36%, and 22% of the cases, respectively. The median Oxford score was 2. The median follow-up duration was 30 months. Ten patients (20%) reached end-stage renal disease. At univariate analysis, HTN, glomerular filtration rate, proteinuria, tubular involvement, and Oxford score >3 were associated with progression to end-stage renal disease (ESRD). Tubular involvement was an independent risk factor for ESRD. Our study confirms the prognostic value of the Oxford classification in immunoglobulin A nephropathy.

Analyses of ultrasound-guided percutaneous pediatric kidney biopsy results: A single center experience

Aim: Percutaneous pediatric kidney biopsies (KB) performed in our center for the past 5 years were evaluated retrospectively. The relationship was examined between histopathological results and variables such as age, gender and ethnicity (Turkish and Syrian children).Material and Methods: A total 330 ultrasound-guided percutaneous pediatric KBs were performed in our center between January 2015 and September 2019. The study included 318 pediatric patients comprising 152 females and 178 males with a mean age of 9.50 ± 4.89 years (range, 2 months- 18 years). Indications, results and complications of the KBs were retrospectively evaluated. Histopathological results were statistically compared between genders and three age groups (0-2, 2-12 and 12-18 years of age). Comparisons were made between the ethnicities and histopathological results.Results: The most common indication for KB was nephrotic syndrome (n: 220, 66.7%). In the biopsy results, the most common primary (n: 230, 69.7%) and secondary (n: 74, 22.4%) glomerular diseases were focal segmental glomerulosclerosis (n: 101, 30.6%) and Henoch-Schonlein purpura nephritis (n: 41, 12.4%), respectively. A statistically significant relationship was determined between the biopsy results and age and gender. No statistically significant relationship was observed between the biopsy results and ethnicity.Conclusion: KB is an important intervention for the identification of glomerular diseases, requiring appropriate treatment in children. The ethnic origin of the patients had no effect on the frequency of the type of the diseases.

SUN-005 Increased urinary exosomal miR-193a indicates primary FSGS possibility and poor prognosis in nephrotic children

Focal segmental glomerulosclerosis (FSGS) is one of the most common primary glomerular diseases causing end-stage renal disease in children. Exosomes are known to mediate intercellular communication by transporting cell-derived proteins and nucleic acids, including various miRNAs. Here we examined the levels of urinary exosomal miR-193a (Uexo-miR-193a) from patients with primary FSGS, and evaluated the values for diagnosis and prognosis.

Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation.

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. The disease generally runs an indolent course but may lead to ESRD in 20–30% of patients in 20 years or more after diagnosis. Patients with IgA nephropathy are ideal candidates for renal transplant because they are generally relatively young and with few comorbidities. Their graft survival is better or comparable to that of controls at 10 years, though few data are available after 10 years of follow-up. Recurrence of the original disease in the graft is a well-known complication of transplant in IgAN and is a significant cause of deterioration of graft function. Recurrent IgAN rarely manifests clinically before 3 years post transplantation. Recurrence rate is estimated to be around 30% with considerable differences among different series. Despite these factors there is no certain recurrence predictor, young age at renal transplant, rapid progression of the original disease and higher levels of circulating galactose-deficient IgA1 and IgA-IgG immune complexes are all associated with a higher rate of recurrence. Which pathogenetic mechanisms are responsible for the progression of the recurrence to graft function deterioration, and what therapy can prevent or slow down the progression of the disease in the graft, are open questions. The aim of this review is to describe the clinical outcome of renal transplantation in IgA patients with attention to the rate and the predictors of recurrence and to discuss the available therapeutic options for the management of recurrence.

Trends of renal diseases in Germany: review of a regional renal biopsy database from 1990 to 2013.

BackgroundSeveral renal biopsy registries in Europe have shown geographical and temporal variations in the patterns of renal diseases. However, there is a lack of current data on trends of renal disease in Central Europe. MethodsAfter exclusion of transplant and re-biopsies, the renal biopsy registry of the German RWTH Aachen University Hospital included data of 1208 biopsies over a period of 24 years (1990–2013). Trends in the biopsy rate and diagnosis of glomerular diseases were analysed. ResultsThe average annual biopsy incidence was 6.1 biopsies per 100 000 population. The frequency of kidney biopsies increased significantly over the years (P < 0.001). Primary glomerulonephritis (GN) accounted for nearly two-thirds (58.4%) of all native kidney biopsies, and immunoglobulin A-nephropathy (IgAN) was the leading histological diagnosis (34.7%) followed by necrotizing GN (RPGN) at 18.7%. IgAN increased 2-fold over the study periods (+195%, P < 0.001). Focal segmental glomerulosclerosis accounted for 6.1% of all diagnoses, and its frequency rose to 3.9-fold (+388%, P < 0.001). Lupus nephritis showed a doubling in incidence (P = 0.0499), while acute tubular necrosis decreased to 3.5-fold (P = 0.0008). All other disease entities failed to exhibit linear trends over time. In children, the most common pathologies were IgAN (26.1%) and minimal change disease (21.7%), whereas RPGN (19.4%) dominated in the group of patients >60 years. ConclusionIgAN was the most common primary glomerular disease in our centre and its prevalence increased over 24 years.

Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerous studies have suggested molecular pathways responsible for the development of FSGS, many still remain unknown about its pathogenic mechanisms. Two important pathways were predicted as candidates for the pathogenesis of FSGS in our previous in silico analysis, whom we aim to confirm experimentally in the present study. Methods: The expression levels of 4 enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediments of biopsy-proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 (COX-2), and prostaglandin I2 synthase. The patients were sub-divided into 2 groups based on the range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. Results: A combined panel of arylsulfatase, hexosaminidase, and COX-2 improved the diagnosis of FSGS by 76%. Hexosaminidase was correlated with the level of proteinuria, while COX-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Conclusion: Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. In addition, these genes can be considered as non-invasive biomarkers for FSGS.

The spectrum of renal diseases observed in native renal biopsies in a single North Indian tertiary care center

We analyzed the spectrum of biopsy-proven renal disease in a single tertiary care center in North India from 2007 to 2016. A total of 420 biopsies were analyzed. Patients were excluded if clinical details were unavailable or if either the histopathology core or the IF core was inadequate. In the final analysis, 359 biopsies were included. All clinical, laboratory, histopathological, and immunofluorescence (IF) findings were recorded in each case. The usefulness of IF in reaching a definitive diagnosis was also analyzed. The patients were in the age range of 2-94 years; 23.1% were children and 76.9% were adults. Males (60.4%) outnumbered females (39.6%) in all the disease categories except lupus nephritis (LN). Primary glomerular diseases (PGDs) (n = 297, 82.7%) were more common than secondary glomerular diseases (SGDs) (n = 46, 12.8%) and tubulointerstitial diseases (n = 16, 4.5%). The most common PGD was focal segmental glomerulosclerosis (FSGS) (23.4%), followed by minimal change disease (17%) and membranous nephropathy (12.5%), whereas the most common SGD was LN, seen in 9.2%. In the present study, IF helped in reaching the final diagnosis in 44.3%. The entities in which IF was most useful in reaching the final diagnoses were FSGS (31.5%) and IgA nephropathy (14.5%). The final pathological diagnosis correlated with the first clinical possibility in 207 of 359 (57.7%) cases. This 10-year study provides descriptive data and highlights the changing pattern of renal disease possibly due to an increased awareness and referral to higher centers.

Serum immunoglobulin G provides early risk prediction in immunoglobulin A nephropathy

BackgroundImmunoglobulin A (IgA) nephropathy (IgAN) is a common primary glomerular disease that potentially leads to renal failure, risk prediction of declining kidney function is crucial for early clinical management. Immunoglobulin G (IgG) is an important constituent of the immune system and serves as the preferred therapeutic target in human autoimmune diseases. However, its role in the progression of IgAN is unclear. MethodsFrom May 2009 to April 2014, 455 patients diagnosed with IgAN at the Second Xiangya Hospital were enrolled in this study; the median follow-up was 42.2 months. All subjects were divided into four groups according to IgG level quartiles. The study endpoint was end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Clinical data and pathological features of renal biopsy specimens were collected. ResultsAmong IgAN patients, serum IgG levels were directly correlated with the levels of serum albumin and serum IgA but reversely correlated with body weight, systolic blood pressure, and serum creatinine and cholesterol levels. According to stratified analysis of serum IgG, the proportions of composite renal endpoints among the enrolled IgAN patients in the serum IgG concentration subgroups 1 (<7.86), 2 (7.86–10.30), 3 (10.31–12.70), and 4 (>12.71 g/l) were 9.6%, 9.2%, 3.7%, and 3.7% respectively. Importantly, cumulative renal survival rates were significantly higher in the patients with increased serum IgG (p = 0.0114). Serum IgG was also predictive of renal survival, with an HR of 0.745 (95% CI, 0.614 to 0.905, p = 0.003) after adjusting for significant factors in the univariate Cox regression and an HR of 0.871 (95% CI, 0.780 to 0.973, p = 0.014) adjusting for traditional risk factors of IgAN. ConclusionThese findings demonstrate that a decreased serum IgG level at the time of renal biopsy is independently associated with a poor renal outcome in IgAN patients.

The Spectrum of Biopsy-Proven Glomerular Diseases among Children in China: A National, Cross-Sectional Survey.

High-quality epidemiologic data on the spectrum of biopsy-proven glomerular diseases among children are limited. This study aimed to determine the profile of and temporal change in biopsy-proven pediatric glomerular diseases in China. We previously conducted a nationwide kidney biopsy survey including 71,151 patients over an 11-year period from January 2004 to December 2014. A total of 7962 children younger than 18 years old from 115 hospitals across China with biopsy-proven glomerular diseases were included in this study. The demographic and clinical variables were extracted from referral records and pathology reports. The composition of pediatric glomerular diseases and clinicopathologic correlations in different sexes, age groups, and regions were assessed. The changing patterns of common glomerulopathies over the study period were examined. Nephrotic syndrome (50%) was the most frequent indication for kidney biopsy in children. Minimal change disease was the most common primary glomerular disease (29%) followed by IgA nephropathy (17%). Henoch-Schonlein purpura nephritis (13%) and lupus nephritis (9%) were the most common secondary glomerular diseases. The proportion of minimal change disease was significant higher in boys (38%) than in girls (13%), whereas lupus nephritis was more prevalent in girls (20%) than in boys (3%). Purpura nephritis (23%) was the major pathologic pattern in younger children (0-12 years old), whereas minimal change disease (33%) was the most common glomerulopathy in adolescents (13-18 years old). The clinicopathologic correlations were slightly different between sexes and age groups. We observed increases in the proportions of minimal change disease, purpura nephritis, and membranous nephropathy over the study period that were contemporaneous with a fall in the proportion of FSGS. The spectrum of glomerular diseases among children varied across sexes, age groups, and regions and changed substantially from 2004 to 2014 in China.

Molecular Mechanisms of Proteinuria in Focal Segmental Glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disease resulting in end-stage renal disease in the USA and is increasing in prevalence worldwide. It is a diverse clinical entity with idiopathic, genetic, metabolic, infectious, and other causes that culminate in a characteristic histologic pattern of injury. Proteinuria is a hallmark of FSGS as well as other primary and secondary glomerular disorders. The magnitude of proteinuria at disease onset and during treatment has prognostic implications for renal survival as well as associated cardiovascular morbidity and mortality. Significant advances over the last two decades have shed light on the molecular architecture of the glomerular filtration barrier. The podocyte is the target cell for injury in FSGS. A growing list of disease-causing gene mutations encoding proteins that regulate podocyte survival and homeostasis has been identified in FSGS patients. Several pathogenic and regulatory pathways have been uncovered that result in proteinuria in rodent models and human FSGS. The recurrence of proteinuria and FSGS after kidney transplantation is supporting evidence for the role of a circulating permeability factor in disease pathogenesis. These advances reviewed herein have significant implications for disease classification and therapeutic drug development for FSGS.

The Spectrum of Glomerulopathies in Kashmir: A Tertiary Care Experience

Background: There is a paucity of data on the spectrum of renal diseases prevalent in the Jammu and Kashmir region. Objectives: To determine the spectrum of glomerulopathies in adult patients attending a tertiary care centre. Methods: Two hundred and twenty-one adequate biopsies from native kidneys of adult patients who presented with features suggestive of glomerular diseases at Sheri Kashmir Institute of medical sciences Srinagar Kashmir for the last 8 years were studied in a retrospective manner. Light and immunofluorescence (IF) microscopy were performed to evaluate these biopsies after obtaining well-informed consent from each patient. Results: Of the 221 biopsies carried out, 150 were performed on males and 71 on females with the mean age of 29 ± 13.5 years. The main presentation was the nephrotic syndrome in 177 (80%), hypertension in 60 (27%), renal insufficiency in 48 (21.7%), and abnormal urinary sediment in 42 (20.3%) of patients. The histopathology revealed minimal change disease (MCD) in 69 (31.2%), membranous glomerulonephritis (MGN) in 48 (21.7%), focal segmental glomerulsclerosis (FSG) in 49 (18%), and mesangioproliferative glomerulonephritis in 16 (7.2%). Patients with atypical presentation of diabetes mellitus showed diabetic nephropathy in 12 (5.4%) patients. Lupus nephritis was in 5 (2.2%) patients. Majority of the patients with MPGN had Immunoglobulin A deposits on IF. While evaluating the underlying cause of MGN, only 1 patient, a 62-year-old male, proved to have adenocarcinoma of the stomach. In the remaining patients, no secondary cause could be found. Thrombotic complications seen in our study were deep venous thrombosis, renal vein thrombosis and middle cerebral artery thrombosis. Conclusion: MCD and MGN were the most common primary glomerular diseases observed in our centre.

Pattern of glomerular disease and clinicopathological correlation: A single-center study from Eastern Nepal.

The pattern of glomerular disease varies worldwide. In the absence of kidney disease/kidney biopsy registry in Nepal, the exact etiology of different forms of glomerular disease is primarily unknown in our country. We analyzed 175 cases of renal biopsies performed from September 2014 to August 2016 in Internal Medicine Ward at B.P. Koirala Institute of Health Sciences. The most common indication for renal biopsy was nephrotic syndrome (34.9%), followed by systemic lupus erythematosus (SLE) with suspected renal involvement (22.3%). Majority of patients were in the 30-60 years' bracket (57.2%), with the mean age of the patients being 35.37 years. The average number of glomeruli per core was 13, with inadequate sampling in 5.1%. Immunoglobulin A (IgA) nephropathy (17%) was found to be the most common primary glomerular disease, followed by membranous nephropathy (14.6%) and focal segmental glomerulosclerosis (14.6%). The most common secondary glomerular disease was lupus nephritis (LN). Complications associated with renal biopsy were pain at biopsy site in 18% of cases, hematuria in 6%, and perinephric hematoma in 4% cases. Although the most common primary glomerular disease was IgA nephropathy, significantly higher population of SLE with LN among Nepalese in comparison with other developing countries warrants further evaluation. As an initial attempt toward documentation of glomerular diseases in the national context, this study should serve as a stepping stone toward the eventual establishment of a full-fledged national registry of glomerular diseases in Nepal.

Spectrum of biopsy-proven renal diseases: A single center experience.

Kidney biopsy is one of the most important tools in the assessment of kidney disease as histopathological diagnosis promotes evidence-based practice in Nephrology. This study included 271 consecutive percutaneous kidney biopsies (145 males and 126 females) performed at EMS Memorial Cooperative Hospital, Perinthalmanna, Kerala, India, from September 2009 to March 2016. Among the biopsy-proven renal diseases (BPRD), primary glomerular diseases (PGD) were the most common (77.78%) followed by secondary glomerular diseases (SGD) (12.22%) and tubulointerstitial diseases (10%). The IgA nephropathy (IgAN) was the most common PGD and majority had mesangial hypercellularity (M1) (93.54%), tubular atrophy (T1 or T2 68.25%), and the most common pattern was M1, E0, S0, and T1, suggesting that patients of Indian subcontinent have aggressive disease type, unlike western literature. The focal segmental glomerulosclerosis (FSGS) was the second most common PGD and the majority were of not otherwise specified type. FSGS, membranous nephropathy and minimal change disease were the three most common causes for PGD causing nephrotic syndrome. Diabetic nephropathy and lupus nephritis were the two most common biopsy-proven SGDs. Among the patients of diabetes mellitus who underwent renal biopsy with suspicion of nondiabetic renal disease (NDRD), 58.33% had NDRD, 16.67% had DN+ NDRD, and 26.67% had DN alone. This study shows the changing pattern BPRD in comparison to earlier studies. This study also confirms the aggressive nature of IgAN in Indian patients and underlines the importance of renal biopsy in patients of DM.

Recent advances of pathogenesis and intervention in pediatric IgA nephropathy

IgA nephropathy (IgAN)is the most common primary glomerular disease, and is one of the most common cause of end-stage renal disease(ESRD). In recent years, the research of the pathogenesis of IgAN has made significant progress, including multi-hit pathogenesis model, genetic heritability factors, complement activation.Effective and specific treatment of IgAN is still lacking, especially for children with IgAN, and there is no guideline.This paper reviewed the recent advances of pathogenesis and intervention in pediatric IgAN. Key words: IgA nephropathy; pathogenesis; interventio; children

Unwinding focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers. The ongoing research is currently focusing on understanding how these molecules and pathways can interplay and be utilized as potential diagnostic and therapeutic targets. Among these molecules, the soluble urokinase plasminogen activating receptor (suPAR) has been studied in detail, both clinically and from a basic science perspective. By now, it has emerged as the earliest and most robust marker of future CKD. Other circulating factors harming podocytes include anti-CD40 auto-antibody and possibly cardiotrophin-like cytokine factor-1. Understanding these factors will aid our efforts to ultimately cure FSGS and possibly treat a larger portion of CKD patients much more effectively.

Abelmoschus manihot \u2013 a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial

BackgroundIgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN.MethodsWe will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks.DiscussionThis study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN.Trial registrationClinicalTrials.gov, identifier: NCT02231125. Registered on 30 August 2014.

Increasing prevalence of membranous nephropathy in patients with primary glomerular diseases: A cross-sectional study in China.

Primary glomerular disease (PGD) remains the most common renal disease in China. A limited number of single centre studies show that the frequency of membranous nephropathy (MN) has increased; however, IgA nephropathy (IgAN) is still the most common PGD. To the best of our knowledge, there has been no multi-centre study in China that has explored the changes in PGD spectrum. To further investigate the changes in renal histopathological spectrum, we performed the cross-sectional study. From June 2010 to May 2015, 5935 patients from 37 hospitals in Shandong Province were involved in this retrospective study. The study was divided into five periods according to 1-year intervals. The patients were divided into four age groups (≤18 years, 19-44 years, 45-59 years and ≥60 years). Among the 5935 qualified specimens, 4855 (81.8%) were diagnosed with PGD. MN (43.3%) became the most common PGD instead of IgA (34.1%) (P < 0.001). The frequency of MN was increased from 30.7% in period 1 to 53.5% in period 5 (P < 0.001). The prevalence of MN tended to increase in every age section. IgA was the main cause of PGD in periods 1 and 2; however, its proportion decreased significantly from 41.8% in period 2 to 25.2% in period 5 (P < 0.001). Primary glomerular disease remains the most common renal disease in our study. For the first time, this cross-sectional study suggests that MN, in place of IgAN, has grown to be the first leading pathological type of PGD.

Clinicopathological Analysis of Glomerular Disease of Adult Onset Nephrotic Syndrome in an Indian Cohort- A Retrospective Study.

Primary glomerular disease presenting with adult onset nephrotic syndrome are a major cause of chronic renal failure worldwide. The spectrum of renal disease presenting with nephrotic syndrome has undergone a gradual change globally over the course of time. However, there still exist regional differences in the incidence of primary glomerular diseases causing adult onset nephrotic syndrome. To observe the spectrum of renal diseases presenting with adult onset nephrotic syndrome with comparative analysis of changing trends over the last five decades with regards to Western and Indian literature. Subjects included patients with age of 18-80 years presenting with nephrotic syndrome. Renal biopsies with immunofluoroscence studies were performed in all patients. Baseline clinical parameters of serum urea, creatinine, albumin, globulin, cholesterol, 24 hour urine protein and urine microscopy were recorded. Descriptive statistics was used and results were expressed as frequencies, percentages, and mean±standard deviation. A total of 227 patients (72% males) were included for the study. Primary glomerular diseases formed 74.01% of total cases and majority of patients included males in the 4th decade. Minimal Change Disease (MCD) (15.8%) including its variants was the most common primary glomerular disease for adult onset of nephrotic syndrome followed by Mesangial proliferative Glomerulonephritis (MSGN) (13.2%). Membranous nephropathy and Type I Membranoproliferative Glomerulonephritis (MPGN) individually accounted for 12.3% of patients. Focal and Segmental Glomerulosclerosis (FSGS) accounted for only 11% of patients. Although, increased incidence of FSGS has been observed worldwide, there exist important regional differences in primary glomerular diseases in Indian population. MCD remains a major glomerular disease for adult onset nephrotic syndrome in different parts of India. Our study over three years represents important data of regional variations of primary glomerular diseases presenting with adult onset nephrotic syndrome.