Kidney Week 2025 Annual Meeting-Clinical-Pathologic-Molecular Correlations in Diabetic Kidney Disease

Video Transcription

Video Summary

This recorded ASN session on “Clinical Pathologic Molecular Correlations in Diabetic Kidney Disease” reviews classic pathology, clinical-pathologic heterogeneity, and emerging prognostic and mechanistic insights beyond traditional glomerular-centric definitions.<br /><br />Charles Jennette summarizes “classic” diabetic kidney disease (DKD) lesions: glomerular and tubular basement membrane thickening (sometimes with lamination/duplication), mesangial matrix expansion progressing to nodular (Kimmelstiel–Wilson) sclerosis and global glomerulosclerosis, plus interstitial fibrosis/tubular atrophy (IFTA). He highlights arteriolar hyalinosis (often both afferent and efferent), mesangiolysis with capillary microaneurysms/hyaline “caps,” and occasional epithelial hyperplasia that can mimic crescents. He discusses linear polyclonal IgG (and albumin) staining along glomerular and tubular basement membranes—common in DKD and sometimes correlated with outcome—then compares DKD with mimics such as idiopathic nodular glomerulosclerosis, monoclonal immunoglobulin deposition disease, and atypical anti-GBM disease, raising questions about whether “trapped” proteins could be pathogenic.<br /><br />Kengo Koichi emphasizes substantial clinical and pathological heterogeneity: many patients do not follow the classic albuminuria-first trajectory, and a large fraction of biopsied diabetics have non-diabetic kidney disease (alone or superimposed). He expands prognostic pathology beyond the RPS classes, noting poor-outcome lesions (e.g., nodules, exudative lesions, mesangiolysis) and a potentially favorable marker, polar vasculosis (neovascularization).<br /><br />Matthew Palmer presents TRIDENT consortium work showing limitations of the RPS classification for prognosis and identifies glomerular epithelial hyperplasia and related lesions (mesangiolysis, exudative lesions, misdirected filtration) as strong predictors. Clustering analyses define a high-risk “cluster 5” characterized by epithelial hyperplasia; adding this feature as an RPS “class 5” modestly improves risk prediction, prompting discussion of podocyte/PEC biology and collapsing-like patterns.<br /><br />Christine Lamont shifts focus to the tubular interstitium: tubular/interstitial lesions occur early (even before albuminuria or eGFR decline) and later correlate strongly with eGFR loss and adverse outcomes. She reviews tubular injury/dysfunction biomarkers (KIM-1, EGF, UMOD, MCP-1, NGAL, proximal tubular secretory scores), their longitudinal worsening in type 1 diabetes cohorts, and their potential to stratify risk and distinguish hemodynamic eGFR changes from true injury. She outlines mechanisms (metabolic reprogramming, hypoxia/mTOR signaling, mitochondrial/autophagy dysfunction, inflammation/fibrosis) and highlights KPMP multi-omic profiling to define maladaptive vs repair tubular cell states and identify drug targets (including effects of SGLT2 inhibitors).

Asset Subtitle

Moderator(s): Frank Brosius, Cynthia Nast

Presentation(s):

Review of the Natural History of Classic Diabetic Glomerulosclerosis - John Charles Jennette
Heterogeneity of Clinical-Pathologic Trajectories in DKD - Kengo Furuichi
Glomerular Epithelial Cell Injury in Diabetes - Matthew Palmer
Importance of the Tubulointerstitium in DKD - Christine Limonte

Meta Tag

Date 11/7/2025

Pathway 1 Diabetic Kidney Disease

Pathway 2 Pathology

Session ID 507260

Keywords

diabetic kidney disease

clinical-pathologic molecular correlations

renal pathology

RPS classification

Kimmelstiel–Wilson nodular sclerosis

mesangial matrix expansion

glomerular basement membrane thickening

tubular basement membrane thickening

interstitial fibrosis and tubular atrophy (IFTA)

arteriolar hyalinosis

mesangiolysis

exudative lesions

glomerular epithelial hyperplasia

tubulointerstitial injury biomarkers

KPMP multi-omics profiling