Observational studyAmerican journal of kidney diseases : the official journal of the National Kidney Foundation2022
Quantification of Glomerular Structural Lesions: Associations With Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome.
Observational study in American journal of kidney diseases : the official journal of the National Kidney Foundation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 23 citations in OpenAlex.
- Urinary clusterin as a biomarker of human kidney disease progression and response to the endothelin receptor antagonist atrasentan: An exploratory analysis from the SONAR trial.Nature communications · 2026Trial
- Single-Nucleus RNA-Sequencing Identifies a Differential Profibrotic Response in Parietal Epithelial Cells in Primary Versus Maladaptive Focal Segmental Glomerulosclerosis.Kidney international reports · 2025Article
- Leveraging complementary multi-omics data integration methods for mechanistic insights in kidney diseases.JCI insight · 2025Article
- Spatial transcriptomics in health and disease.Nature reviews. Nephrology · 2024Review
- Precision Medicine in Nephrology: An Integrative Framework of Multidimensional Data in the Kidney Precision Medicine Project.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Article
- Type I IFN in Glomerular Disease: Scarring beyond the STING.International journal of molecular sciences · 2024Review
- Rationale and design of the Nephrotic Syndrome Study Network (NEPTUNE) Match in glomerular diseases: designing the right trial for the right patient, today.Kidney international · 2024Article
- Proteomic profiling of kidney biopsies in nephrotic syndrome.Wellcome open research · 2024Article
- Identification of Glomerular and Plasma Apolipoprotein M as Novel Biomarkers in Glomerular Disease.Kidney international reports · 2023Article
- Present and future directions in diabetic kidney disease.Journal of diabetes and its complications · 2022Review
- Defining diagnostic trajectories in patients with podocytopathies.Clinical kidney journal · 2022Review
- Mechanisms of podocyte injury and implications for diabetic nephropathy.Clinical science (London, England : 1979) · 2022Article
- Clinical Outcomes in the Nephrotic Syndrome Study Network: Disease Burden and Treatment Patterns over Time.Glomerular diseasesArticle
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Authors and funding
18 authors at 9 institutions in 1 country.
Funding
Abstract
RATIONALE &
objectiveThe current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies nor the clinical and molecular heterogeneity of these diseases. STUDY
designProspective observational cohort study. SETTING &
participants221 MCD and FSGS patients enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). EXPOSURE: The NEPTUNE Digital Pathology Scoring System (NDPSS) was applied to generate scores for 37 glomerular descriptors. OUTCOME: Time from biopsy to complete proteinuria remission, time from biopsy to kidney disease progression (40% estimated glomerular filtration rate [eGFR] decline or kidney failure), and eGFR over time. ANALYTICAL APPROACH: Cluster analysis was used to group patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for associations with outcomes using adjusted Cox models and linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes between clusters and identify genes associated with individual descriptors driving cluster membership.
resultsThree clusters were identified: X (n = 56), Y (n = 68), and Z (n = 97). Clusters Y and Z had higher probabilities of proteinuria remission (HRs of 1.95 [95% CI, 0.99-3.85] and 3.29 [95% CI, 1.52-7.13], respectively), lower hazards of disease progression (HRs of 0.22 [95% CI, 0.08-0.57] and 0.11 [95% CI, 0.03-0.45], respectively), and lower loss of eGFR over time compared with X. Cluster X had 1,920 genes that were differentially expressed compared with Y+Z; these reflected activation of pathways of immune response and inflammation. Six descriptors driving the clusters individually correlated with clinical outcomes and gene expression. LIMITATIONS: Low prevalence of some descriptors and biopsy at a single time point.
conclusionsThe NDPSS allows for categorization of FSGS/MCD patients into clinically and biologically relevant subgroups, and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems.
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