Validation of the Oxford classification of IgA nephropathy for pediatric patients from China

BACKGROUND: The Oxford classification of IgA nephropathy (IgAN) provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations. METHODS: A total of 218 children with IgAN from 7 renal centers in China were enrolled. The inclusion criteria was similar to the original Oxford study. RESULTS: There were 98 patients (45%) with mesangial proliferation (M1), 51 patients (23%) with endocapillary proliferation (E1), 136 patients (62%) with segmental sclerosis/adhesion lesion (S1), 13 patients (6%) with moderate tubulointerstitial fibrosis (T1 26-50% of cortex scarred), and only 2 patients (1%) with severe tubulointerstitial fibrosis (T2, >50% of cortex scarred). During a median follow-up duration of 56 months, 24 children (12.4%) developed ESRD or 50% decline in renal function. In univariate COX analysis, we found that tubular atrophy/interstitial fibrosis (HR 4.3, 95%CI 1.8-10.5, P < 0.001) and segmental glomerulosclerosis (HR 9.2 1.2-68.6, P = 0.03) were significant predictors of renal outcome. However, mesangial hypercellularity, endocapillary proliferation, crescents, and necrosis were not associated with renal prognosis. In the multivariate COX regression model, none of these pathologic lesions were shown to be independent risk factors of unfavorable renal outcome except for tubular atrophy/interstitial fibrosis (HR 2.9, 95%CI 1.0-7.9 P = 0.04). CONCLUSIONS: We confirmed tubular atrophy/interstitial fibrosis was the only feature independently associated with renal outcomes in Chinese children with IgAN

Combatting global grassland degradation

Grasslands are under severe threat from ongoing degradation, undermining their capacity to support biodiversity, ecosystem services and human well-being. Yet, grasslands are largely ignored in sustainable development agendas. In this Perspective, we examine the current state of global grasslands and explore the extent and dominant drivers of their degradation. Socio-ecological solutions are needed to combat degradation and promote restoration. Important strategies include: increasing recognition of grasslands in global policy; developing standardized indicators of degradation; using scientific innovation for effective restoration at regional and landscape scales; and enhancing knowledge transfer and data sharing on restoration experiences. Stakeholder needs can be balanced through standardized assessment and shared understanding of the potential ecosystem service trade-offs in degraded and restored grasslands. The integration of these actions into sustainability policy will aid in halting degradation and enhancing restoration success, and protect the socio-economic, cultural and ecological benefits that grasslands provide

Regulon analysis identifies protective FXR and CREB5 in proximal tubules in early diabetic kidney disease

Abstract Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and a leading cause of kidney failure worldwide. Despite its prevalence, the mechanisms underlying early kidney damage in DKD remain poorly understood. In this study, we used single nucleus RNA-seq to construct gene regulatory networks (GRNs) in the kidney cortex of patients with early DKD. By comparing these networks with those of healthy controls, we identify cell type-specific changes in genetic regulation associated with diabetic status. The regulon activities of FXR (NR1H4) and CREB5 were found to be upregulated in kidney proximal convoluted tubule epithelial cells (PCTs), which were validated using immunofluorescence staining in kidney biopsies from DKD patients. In vitro experiments using cultured HK2 cells showed that FXR and CREB5 protected cells from apoptosis and epithelial–mesenchymal transition. Our findings suggest that FXR and CREB5 may be promising targets for early intervention in patients with DKD

Clinical features of anemia in membranous nephropathy patients: a Chinese cohort study

AbstractBackground Anemia is a common complication in patients with progressive chronic kidney disease. This cohort study evaluated the prevalence, clinical features and prognosis of membranous nephropathy (MN) with anemia.Methods We retrospectively analyzed a cohort of MN patients diagnosed using renal biopsy between February 2012 and February 2018. The clinical and pathological characteristics at baseline were recorded, and the outcomes (hemoglobin, proteinuria and renal function) during follow-ups were also evaluated. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for anemia in MN patients. The MN patients were divided according to the therapeutic effect they experienced as follows: without-anemia, completely corrected anemia, standard anemia treatment and nonstandard anemia treatment groups. We compared the rate of complete remission of MN and renal end-point events among the four groups.Results The median age of 483 patients was 42.43 (26.59, 50.20) years at the time of MN diagnosis. The prevalence of anemia at baseline was 23.81%, and the cumulative prevalence was 50.72%. There were 133 cases of mild anemia, 103 cases of moderate anemia and 9 cases of severe anemia; in addition, there were 228 cases of normocytic anemia and 17 cases of microcytic hypochromic anemia. Multivariate logistic regression indicated that acute renal tubule injury >5% (OR = 1.634, 95% CI 1.034, 2.581; p = 0.035), total protein level (OR = 0.949, 95% CI 0.923, 0.975; p < 0.001), cholesterol level (OR = 0.833, 95% CI 0.749, 0.926, p = 0.001), hypokalemia (OR = 2.612, 95% CI 1.227, 5.560, p = 0.013) and hypophosphatemia (OR = 2.653, 95% CI 1.303, 5.403, p = 0.007) were independent risk factors for anemia in MN patients. The complete remission rate of MN patients without anemia was significantly higher than that of anemia patients who exhibited treatment failure. The incidence of renal endpoint events was different among the four groups.Conclusion The anemia experienced by MN patients is mainly mild and moderate, normocytic anemia. The pathological features of acute renal tubular injury and clinical nutritional status are independent risk factors for anemia. There were differences in renal prognosis among anemia patients with different treatment outcomes

Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

Objective. To investigate potential drugs for diabetic nephropathy (DN) using whole-genome expression profiles and the Connectivity Map (CMAP). Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs) between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1) A total of 1065 DEGs (FDR < 0.05 and fold change > 1.5) were found in late stage DN patients compared with early stage DN patients. (2) Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2), vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs), PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN

Quantitative susceptibility mapping of articular cartilage in patients with osteoarthritis at 3T

BackgroundQuantitative susceptibility mapping (QSM) has recently been applied in humans to quantify the magnetic susceptibility of collagen fibrils in the articular cartilage.PurposeTo determine the ability of QSM to detect cartilage matrix degeneration between normal and early knee osteoarthritis (OA) patients.Study typeProspective.PopulationTwenty-four patients with knee OA and 24 age- and sex-matched healthy controls.Field strength/sequence3D gradient echo, T1 turbo spin echo, and proton density-weighted (PDw) spectral attenuated inversion recovery (SPAIR) sequence at 3.0T.AssessmentScan-rescan reproducibility of the susceptibility values in the cartilage was assessed in control subjects. Cartilage thickness, volume, mean, and standard deviation (SD) of susceptibility values of the cartilage compartments were compared between normal and OA patients. The relationship between magnetic susceptibility values and cartilage lesion grading based on MR images was studied.Statistical testsThe Wilcoxon Rank-Sum test was used to compare cartilage thickness, volume, mean, and SD of susceptibility values between control subjects and OA patients. A Spearman rank correlation was performed to study the relationship between the mean and SD of susceptibility values and the cartilage thinning grades.ResultsThe SD of magnetic susceptibility values in the knee cartilage was significantly lower in OA patients compared with healthy controls, and it decreased with more severe MR grades of cartilage thinning degeneration. Significant correlations between the SD of susceptibility values and cartilage thinning grades were observed with R2  = 0.64 and P = 0.000, R2  = 0.47 and P = 0.002, R2  = 0.52 and P = 0.001, R2  = 0.42 and P = 0.0006, and R2  = 0.67 and P = 0.000 for medial femoral condyle (MFC), lateral femoral condyle (LFC), medial tibia (MT), lateral tibia (LT), and patella, respectively. No significant difference was found in cartilage volume (P = 0.17, P = 0.13, P = 0.20, P = 0.25, and P = 0.18 for MFC, LFC, MT, LT, and patella, respectively) and thickness (P = 0.31, P = 0.19, P = 0.16, P = 0.09, and P = 0.22 for MFC, LFC, MT, LT, and patella, respectively) between OA patients and healthy controls.Data conclusionThe variations of susceptibility values in the knee cartilage decrease with the degree of cartilage degeneration. QSM may be a sensitive indicator for alteration of the collagen network and shows potential to detect cartilage degeneration at early stage.Level of evidence2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018