What conditions are vanishing glomeruli typically seen in?

Vanishing Glomeruli: Clinical Conditions and Pathological Context

Primary Conditions Associated with Vanishing Glomeruli

Vanishing glomeruli (globally sclerotic glomeruli) are most characteristically seen in advanced chronic kidney disease, particularly in the end-stage of focal segmental glomerulosclerosis (FSGS), chronic lupus nephritis (Class VI), and conditions causing progressive nephron loss through ischemic injury or chronic glomerular damage. 1

End-Stage FSGS and Progressive Glomerulosclerosis

• FSGS represents the most common glomerular cause leading to ESKD, with vanishing glomeruli developing as the final stage of progressive nephron destruction 2
• The evolution from segmental sclerosis to global sclerosis follows two distinct pathways: Pathway I involves concurrent development of global sclerosis with tubular degeneration, terminating in global and cylindrical remnants of extracellular matrix surrounded by abundant fibrous tissue 3
• Pathway II demonstrates tubular degeneration ahead of glomerular damage progression, leading to atubular glomerular cysts 3
• Approximately 50% of nephrotic FSGS patients progress to ESRD over 3-8 years, with global sclerosis representing the terminal histological finding 4

Lupus Nephritis Class VI

• Class VI lupus nephritis is defined by advanced sclerotic changes with ≥90% globally sclerotic glomeruli resulting from preceding active lupus lesions 1
• The International Society of Nephrology/Renal Pathology Society recognizes that Class VI is rarely seen in renal biopsy specimens, as patients typically present earlier in their disease course 1
• Distinguishing globally sclerotic glomeruli from lupus nephritis versus other causes (aging, hypertension, healed thrombotic microangiopathy) remains challenging and requires evidence such as residual immune deposits (other than IgM and C3) by immunofluorescence or features like fragmented tuft with surrounding fibrosis and extensive disruption of Bowman's capsule 1

Ischemic and Age-Related Nephropathy

• Ischemic glomeruli demonstrate characteristic features including subcapsular clusters with ischemic tuft collapse surrounded by collagen in Bowman's space, representing arterionephrosclerosis rather than primary glomerular disease 1
• Morphometric studies demonstrate that obstructive hyaline arteriolosclerosis leads to smaller glomeruli with increased periglomerular extracellular matrix, consistent with ischemic global sclerosis 5
• In aging kidneys, approximately 29.1% of normal glomeruli show associated hyaline arteriolosclerosis, which can progress to global sclerosis through ischemic mechanisms 5

Pathological Reporting Considerations

Documentation Requirements

• The number of globally sclerosed glomeruli must be explicitly stated in pathology reports, along with the total number of glomeruli examined 1
• Globally sclerotic glomeruli should be distinguished from segmentally sclerosed glomeruli, as this distinction has prognostic implications 1
• When evaluating chronicity indices, globally sclerotic glomeruli with typical patterns of arterionephrosclerosis should not be attributed to the primary glomerular disease 1

Critical Diagnostic Pitfalls

• Segmental staining for IgM, C3, and occasionally C1q is common in areas of segmental sclerosis and should not be interpreted as evidence of immune-complex glomerulonephritis 1
• IgM and/or C3 deposition in FSGS has low incidence (28.3%) and does not significantly alter histological parameters, though it may be associated with longer disease duration and higher pre-treatment serum creatinine 6
• Up to 20% of renal transplant patients may have simultaneous nephrotoxicity and rejection, making distinction between cyclosporine-associated nephropathy (which can cause progressive glomerular loss) and rejection challenging 7

Prognostic Implications

• The percentage of globally sclerotic glomeruli correlates directly with progression to ESRD, with severe global sclerosis (>50%) indicating poor prognosis 1, 4
• Interstitial fibrosis ≥20% combined with elevated serum creatinine (>1.3 mg/dL) and persistent proteinuria represent the most significant positive predictors of progression to ESRD in FSGS 4
• Cyclosporine-associated structural nephrotoxicity can cause progressive nephron loss with 5-15% of transplant recipients showing serial deterioration despite dose reduction, characterized by striped interstitial fibrosis with tubular atrophy and eventual global glomerulosclerosis 7