Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

BACKGROUND: Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. METHODS: We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. RESULTS: Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan-Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835-76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078-0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047-0.689; p = 0.012) was further reduced. CONCLUSIONS: NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

Comparative Analysis of Gut Microbial Composition and Functions in Przewalski's Gazelle (Procapra przewalskii) From Various Habitats.

Gut microbiota of mammals participates in host nutrient metabolism and plays an important role in host adaptation to the environment. Herein, to understand the relationship between environment differences and the composition and abundance of the gut microbiota of Przewalski's gazelle (Procapra przewalskii) in almost all its habitats, high throughput sequencing of the 16S rRNA gene was used to compared the characteristics of the gut microbiota based on total 120 fecal samples. The results showed that Przewalski's gazelle exhibited different characteristics of microbiota diversity in different habitats. The Jiangxigou Rescue Station (JX), Nongchang (NC), and Ganzihe and Haergai townships (GH) groups had a relatively high microbiota diversity, while the Niaodao scenic area (ND) group had the lowest diversity. This finding seemed to follow a similar pattern of change in the population of Przewalski's gazelle. Bacteroidetes and Actinobacteria were the phyla with significant differences, especially between the Wayu township (WY) and the other groups. The difference in the microbiota mainly included the Ruminococcaceae UCG-005, Christensenellaceae R-7 group, and Bacteroidaceae and was enriched in the ND, WY, and other regions. We speculated that the difference in the gut microbiota was due to a difference in environmental characteristics, particularly the food resources that the host can obtain. We speculated that a similar microbiome has important functions for species survival and represents the evolutionary commonality of Przewalski's gazelle, while a different microbiome plays an important role in the adaptation of Przewalski's gazelle to a different environment. The results of this study illustrate how the same species adapts to different environments from the perspective of gut microbiota plasticity and therefore are of great significance for the protection and restoration of the population of this species.

Prediction of prognosis in immunoglobulin a nephropathy patients with focal crescent by machine learning.

BACKGROUND AND OBJECTIVES: Immunoglobulin a nephropathy (IgAN) is the most common primary glomerular disease in the world, with different clinical manifestations, varying severity of pathological changes, common complications of crescent formation in different proportions, and great individual heterogeneous in clinical outcomes. Therefore, we aim to develop a machine learning (ML) based predictive model for predicting the prognosis of IgAN with focal crescent formation and without obvious chronic renal lesions (glomerulosclerosis <25%). MATERIALS: We retrospectively reviewed biopsy-proven IgAN patients in our hospital and cooperative hospital from 2005 to 2017. The method of feature importance of random forest (RF) was applied to conduct feature exploration of feature variables to establish the characteristic variables that are closely related to the prognosis of focal crescent IgAN. Multiple ML algorithms were attempted to establish the prediction models. The area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC) were applied to evaluate the predictive performance via three-fold cross validation (namely 2 training sets and 1 validation set). RESULTS: RF was used to screen the important features, the top three of which were baseline estimated glomerular filtration rate (eGFR), serum creatine and triglyceride. Ten important features were selected as important predictors for modeling on the basis of data-driven and medical selection, predictors include: age, baseline eGFR, serum creatine, serum triglycerides, complement 3(C3), proteinuria, mean arterial pressure (MAP) and Hematuria, crescents proportion of glomeruli, Global crescent proportion of glomeruli. In a variety of ML algorithms, the support vector machine (SVM) algorithm displayed better predictive performance, with Precision of 0.77, Recall of 0.77, F1-score of 0.73, accuracy of 0.77, AUROC of 79.57%, and AUPRC of 76.5%. CONCLUSIONS: The SVM model is potentially useful for predicting the prognosis of IgAN patients with focal crescent shape and without obvious chronic renal lesions.

The role of urine IgG in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis.

BACKGROUND: IgA nephropathy (IgAN), the most common glomerulonephritis in the world, is an important cause of end-stage renal disease (ESRD). It is necessary to explore new prognostic markers for predicting the activity and progress of IgAN. There are few studies on new prognostic markers in IgAN patients with high proportion of glomerulosclerosis. This study aims to explore the value of urine IgG in predicting the prognosis of IgAN patients. METHODS: The primary end point of this retrospective study was a composite event with a reduction in estimated glomerular filtration rate (eGFR) of ≥ 50% or ESRD or death. This study assessed the association between urinary IgG and clinicopathological parameters, as well as the prognosis of a high proportion of patients with global glomerulosclerotic IgAN. RESULTS: This study included 105 IgAN patients with high proportion of global glomerulosclerotic. The level of urinary protein IgG was significantly correlated with clinical prognostic factors. The level of urinary protein IgG was positively correlated with urinary protein excretion (rs = 0.834, P < 0.001), CRP (rs = 0.375, P < 0.001), and C4 (rs = 0.228, P = 0.019), and negatively correlated with eGFR (rs = - 0.307, P = 0.001). In addition, the level of urinary IgG increased with the increase of tubulointerstitial injury rate, which was positively correlated with endothelial cell proliferation and crescent (all P < 0.05). Prognostic analysis using the Cox proportional hazard regression model and Kaplan-Meier survival curve further determined that urine IgG is an independent risk factor for the prognosis of IgAN with high proportion of global glomerulosclerosis. CONCLUSIONS: This study determined that urine IgG can be used as a useful predictor of the prognosis of IgAN patients with high proportion global glomerulosclerosis. The mechanism of urine IgG trends in IgAN with high proportion of glomerulosclerosis needs further study.

Effect of magnetic powder on membrane fouling mitigation and microbial community/composition in membrane bioreactors (MBRs) for municipal wastewater treatment.

This study aims to investigate the usefulness of magnetic powder addition in membrane bioreactors (MBRs) for membrane fouling mitigation and its effect on microbial community and composition. The comparison between the two MBRs (one with magnetic powder (MAS-MBR) and one without magnetic powder (C-MBR)) was carried out to treat synthetic municipal wastewater. Results showed that bioflocculation and adsorption of magnetic powder contributed only minimally to membrane fouling mitigation while the slower fouling rate might be ascribed to magnetic bio-effect. The macromolecules (larger than 500 kDa and 300-500 kDa) of soluble microbial product from the MAS-MBR were reduced by 24.06% and 11.11%, respectively. High-throughput sequencing demonstrated the most abundant genera of biofilm sludge indicated lower abundance in bulk sludge from the MAS-MBR compared to the C-MBR. It is possible that less membrane fouling is connected to reductions in large molecules and pioneer bacteria from bulk sludge.

Movements of wild ruddy shelducks in the Central Asian Flyway and their spatial relationship to outbreaks of highly pathogenic avian influenza H5N1.

Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease.

Wild bird migration across the Qinghai-Tibetan plateau: a transmission route for highly pathogenic H5N1.

BACKGROUND: Qinghai Lake in central China has been at the center of debate on whether wild birds play a role in circulation of highly pathogenic avian influenza virus H5N1. In 2005, an unprecedented epizootic at Qinghai Lake killed more than 6000 migratory birds including over 3000 bar-headed geese (Anser indicus). H5N1 subsequently spread to Europe and Africa, and in following years has re-emerged in wild birds along the Central Asia flyway several times. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the potential involvement of wild birds in the spread of H5N1, we studied the movements of bar-headed geese marked with GPS satellite transmitters at Qinghai Lake in relation to virus outbreaks and disease risk factors. We discovered a previously undocumented migratory pathway between Qinghai Lake and the Lhasa Valley of Tibet where 93% of the 29 marked geese overwintered. From 2003-2009, sixteen outbreaks in poultry or wild birds were confirmed on the Qinghai-Tibet Plateau, and the majority were located within the migratory pathway of the geese. Spatial and temporal concordance between goose movements and three potential H5N1 virus sources (poultry farms, a captive bar-headed goose facility, and H5N1 outbreak locations) indicated ample opportunities existed for virus spillover and infection of migratory geese on the wintering grounds. Their potential as a vector of H5N1 was supported by rapid migration movements of some geese and genetic relatedness of H5N1 virus isolated from geese in Tibet and Qinghai Lake. CONCLUSIONS/SIGNIFICANCE: This is the first study to compare phylogenetics of the virus with spatial ecology of its host, and the combined results suggest that wild birds play a role in the spread of H5N1 in this region. However, the strength of the evidence would be improved with additional sequences from both poultry and wild birds on the Qinghai-Tibet Plateau where H5N1 has a clear stronghold.

Bird migration and risk for H5N1 transmission into Qinghai Lake, China.

The highly pathogenic avian influenza H5N1 virus still cause devastating effects to humans, agricultural poultry flocks, and wild birds. Wild birds are also detected to carry H5N1 over long distances and are able to introduce it into new areas during migration. In this article, our objective is to provide lists of bird species potentially involved in the introduction of highly pathogenic avian influenza H5N1 in Qinghai Lake, which is an important breeding and stopover site for aquatic birds along the Central Asian Flyway. Bird species were classified according to the following behavioral and ecological factors: migratory status, abundance, degree of mixing species and gregariousness, and the prevalence rate of H5N1 virus. Most of the high-risk species were from the family Anatidae, order Anseriformes (9/14 in spring, 11/15 in fall). We also estimated the relative risk of bird species involved by using a semi-quantitative method; species from family Anatidae accounted for over 39% and over 91% of the total risk at spring and fall migration periods, respectively. Results also show the relative risk for each bird aggregating site in helping to identify high-risk areas. This work may also be instructive and meaningful to the avian influenza surveillance in the breeding, stopover, and wintering sites besides Qinghai Lake along the Central Asian Flyway.

Flying over an infected landscape: distribution of highly pathogenic avian influenza H5N1 risk in South Asia and satellite tracking of wild waterfowl.

Highly pathogenic avian influenza (HPAI) H5N1 virus persists in Asia, posing a threat to poultry, wild birds, and humans. Previous work in Southeast Asia demonstrated that HPAI H5N1 risk is related to domestic ducks and people. Other studies discussed the role of migratory birds in the long distance spread of HPAI H5N1. However, the interplay between local persistence and long-distance dispersal has never been studied. We expand previous geospatial risk analysis to include South and Southeast Asia, and integrate the analysis with migration data of satellite-tracked wild waterfowl along the Central Asia flyway. We find that the population of domestic duck is the main factor delineating areas at risk of HPAI H5N1 spread in domestic poultry in South Asia, and that other risk factors, such as human population and chicken density, are associated with HPAI H5N1 risk within those areas. We also find that satellite tracked birds (Ruddy Shelduck and two Bar-headed Geese) reveal a direct spatio-temporal link between the HPAI H5N1 hot-spots identified in India and Bangladesh through our risk model, and the wild bird outbreaks in May-June-July 2009 in China (Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl.