Quantitative morphometrics reveals glomerular changes in patients with infrequent segmentally sclerosed glomeruli

Area of Science:

• Nephrology
• Pathology
• Quantitative Morphology

Background:

• Focal segmental glomerulosclerosis (FSGS) diagnosis relies on detecting segmentally sclerosed glomeruli (SSG) in kidney biopsies.
• Rare SSG may be missed, leading to underdiagnosis of FSGS.
• The utility of quantitative morphometrics in unaffected glomeruli for detecting infrequent SSG is not well understood.

Purpose of the Study:

• To investigate whether quantitative morphometrics in glomeruli without pathological phenotypes can identify patients with infrequent SSG.
• To assess the diagnostic performance of morphometric parameters in detecting FSGS.

Main Methods:

• Quantitative morphometrics were performed on glomeruli without pathological findings in large kidney sections from 137 patients.
• Multivariate modeling identified morphometrics associated with SSG frequency.
• Receiver Operator Curve (ROC) analysis determined the ability of morphometrics to identify FSGS patients.

Main Results:

• Over half of patients (51.8%) had at least one SSG, with 30% having infrequent lesions (<2% of glomeruli).
• Decreased podocyte density and increased mesangial index were independently associated with higher SSG frequency.
• Podocyte density (AUC 0.77) and mesangial index (AUC 0.79) showed potential in identifying FSGS patients with infrequent SSG.

Conclusions:

• Quantitative morphometrics in unaffected glomeruli, specifically podocyte density and mesangial index, can identify patients with infrequent SSG.
• These morphometric parameters may serve as valuable clinical markers for diagnosing FSGS when SSG are rare.